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onsdag 25 januari 2017

Connexiini kanavat, glukoosi ja inositolijohdannaiset?

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Items: 3

Casas M, Buvinic S, Jaimovich E.
Exerc Sport Sci Rev. 2014 Jul;42(3):110-6. doi: 10.1249/JES.0000000000000017. Review.


Tetanic electrical stimulation releases adenosine triphosphate (ATP) from muscle fibers through pannexin-1 channels in a frequency-dependent manner; extracellular ATP activates signals that ultimately regulate gene expression and is able to increase glucose transport through activation of P2Y receptors, phosphatidylinositol 3-kinase, Akt, and AS160. We hypothesize that this mechanism is an important link between exercise and the regulation of muscle fiber plasticity and metabolism.
Orellana JA, Sáez PJ, Cortés-Campos C, Elizondo RJ, Shoji KF, Contreras-Duarte S, Figueroa V, Velarde V, Jiang JX, Nualart F, Sáez JC, García MA.
Glia. 2012 Jan;60(1):53-68. doi: 10.1002/glia.21246.


The ventromedial hypothalamus is involved in regulating feeding and satiety behavior, and its neurons interact with specialized ependymal-glial cells, termed tanycytes. The latter express glucose-sensing proteins, including glucose transporter 2, glucokinase, and ATP-sensitive K(+) (K(ATP) ) channels, suggesting their involvement in hypothalamic glucosensing. Here, the transduction mechanism involved in the glucose-induced rise of intracellular free Ca(2+) concentration ([Ca(2+) ](i) ) in cultured β-tanycytes was examined. Fura-2AM time-lapse fluorescence images revealed that glucose increases the intracellular Ca(2+) signal in a concentration-dependent manner. Glucose transportation, primarily via glucose transporters, and metabolism via anaerobic glycolysis increased connexin 43 (Cx43) hemichannel activity, evaluated by ethidium uptake and whole cell patch clamp recordings, through a K(ATP) channel-dependent pathway. Consequently, ATP export to the extracellular milieu was enhanced, resulting in activation of purinergic P2Y(1) receptors followed by inositol trisphosphate receptor activation and Ca(2+) release from intracellular stores. The present study identifies the mechanism by which glucose increases [Ca(2+) ](i) in tanycytes. It also establishes that Cx43 hemichannels can be rapidly activated under physiological conditions by the sequential activation of glucosensing proteins in normal tanycytes.
Free PMC Article
Niessen H, Harz H, Bedner P, Krämer K, Willecke K.
J Cell Sci. 2000 Apr;113 ( Pt 8):1365-72.


Intercellular propagation of signals through connexin32-containing gap junctions is of major importance in physiological processes like nerve activity-dependent glucose mobilization in liver parenchymal cells and enzyme secretion from pancreatic acinar cells.
 In these cells, as in other organs, more than one type of connexin is expressed.

 We hypothesized that different permeabilities towards second messenger molecules could be one of the reasons for connexin diversity. In order to investigate this, we analyzed transmission of inositol 1,4,5-trisphosphate-mediated calcium waves in FURA-2-loaded monolayers of human HeLa cells expressing murine connexin26, -32 or -43. Gap junction-mediated cell coupling in different connexin-transfected HeLa cells was standardized by measuring the spreading of microinjected Mn(2+) that led to local quenching of FURA-2 fluorescence. Microinjection of inositol 1,4,5-trisphosphate into confluently growing HeLa connexin32 transfectants induced propagation of a Ca(2+) wave from the injected cell to neighboring cells that was at least three- to fourfold more efficient than in HeLa Cx26 cells and about 2.5-fold more efficient than in HeLa Cx43 transfectants. Our results support the notion that diffusion of inositol 1,4,5-trisphosphate through connexin32-containing gap junctions is essential for the optimal physiological response, for example by recruiting liver parenchymal cells that contain subthreshold levels of this short lived second messenger.
Free Article

tisdag 24 januari 2017

Defosforylaatioaspekti: MINPP1 ja paradokaalisesti IP6K defosoryloi. ATP/ADP merkitsevä

LÄHDE: Biochem J. 2014 Aug 15;462(1):173-84. doi: 10.1042/BJ20130992.

Discovery of InsP6-kinases as InsP6-dephosphorylating enzymes provides a new mechanism of cytosolic InsP6 degradation driven by the cellular ATP/ADP ratio.


InsP6 (inositol hexakisphosphate), the most abundant inositol phosphate in metazoa, is pyrophosphorylated to InsP7 [5PP-InsP5 (diphosphoinositol pentakisphosphate)] by cytosolic and nuclear IP6Ks (InsP6 kinases) and to 1PP-InsP5 by another InsP6/InsP7 kinase family.

 MINPP1 (multiple inositol-polyphosphate phosphatase 1), the only known InsP6 phosphatase, is localized in the ER (endoplasmic reticulum) and lysosome lumina.

 A mechanism of cytosolic InsP6 dephosphorylation has remained enigmatic so far. In the present study, we demonstrated that IP6Ks change their kinase activity towards InsP6 at a decreasing ATP/ADP ratio to an ADP phosphotransferase activity and dephosphorylate InsP6.

 Enantio-selective analysis revealed that Ins(2,3,4,5,6)P5 is the main InsP5 product of the IP6K reaction, whereas the exclusive product of MINPP1 activity is the enantiomer Ins(1,2,4,5,6)P5.

Whereas lentiviral RNAi-based depletion of MINPP1 at falling cellular ATP/ADP ratios had no significant impact on Ins(2,3,4,5,6)P5 production, the use of the selective IP6K inhibitor TNP [N2-(m-trifluorobenzyl),N6-(p-nitrobenzyl)purine] abolished the production of this enatiomer in different types of cells.

 Furthermore, by analysis of rat tissue and human blood samples all (main and minor) dephosphorylation products of InsP6 were detected in vivo.

 In summary, we identified IP6Ks as novel nuclear and cytosolic InsP6- (and InsP5-) dephosphorylating enzymes whose activity is sensitively driven by a decrease in the cellular ATP/ADP ratio, thus suggesting a role for IP6Ks as cellular adenylate energy 'sensors'.
[PubMed - indexed for MEDLINE]

IP6K1 geeni, Kr. 3p21.31.

IP6K1 geeni, kromosomi 3p21.31.

IP6K1 inositol hexakisphosphate kinase 1 [ Homo sapiens (human) ]

 Tämä geeni IP6K1  kuuluu inositolifosfokinaasien perheesen.  Sen koodaama proteiini saattaa vastata inositoli-6- fosfaatin ( fytiinin, IP6) konvertoitumista  difosfo-inositoli-penta-cis-fosfaatiksi  IP7/ PP-IP5. Se saattaa  myös konvertoida  1,3,4,5,6- pentakisfosfaatin (IP5)  muotoon PP-IP4, joka on IP6 variantti.  On kuvattu alternatiivisesti pleissautunut transkriptivariantti.

Gene ID: 9807, updated on 19-Jan-2017
Official Symbol
IP6K1 provided by HGNC
Official Full Name
inositol hexakisphosphate kinase 1provided by HGNC
Primary source
See related
Ensembl:ENSG00000176095 MIM:606991; Vega:OTTHUMG00000158197
Gene type
protein coding
RefSeq status
Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
This gene encodes a member of the inositol phosphokinase family. The encoded protein may be responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]

LISÄTIETOA artikkeleissa

Related articles in PubMed

  1. PiUS (Pi uptake stimulator) is an inositol hexakisphosphate kinase. Schell MJ, et al. FEBS Lett, 1999 Nov 19. PMID 10567691
  2. Localization of PiUS, a stimulator of cellular phosphate uptake to human chromosome 3p21.3. White KE, et al. Somat Cell Mol Genet, 1998 Jan. PMID 9776982
See all (26) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

  1. IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus
    Muistiin 24.1. 2017

IP6K2 geeni, Kr. 3p21.31.

IP6K2 geeni, kr. 3.

IP6K2 fosforyloi inositolihexakisfosfaattia IP7- muotoon, jolloin se on IP5-pyrofosfaattia . Sitä merkitään joko IP7:ksi.
Mahdollisesti se voi konvertoida myös IP5 muodon, jossa on inositolirenkaan fosfaatit asemissa 1,3,4,5,6, muotoon PP-Ins4, difosfoinositol-tetrakisfosfaatti , jolloin se on IP4- pyrofosfaattia. Ja vaikuttaa kasvusupressiota ja IFN-beetan apoptoottisia aktiivisuuksia joissain ovariaalisyövissä.
diphosphoinositol pentakisphosphate (InsP7/PP-InsP5)
P6K2 inositol hexakisphosphate kinase 2 [ Homo sapiens (human) ]
Gene ID: 51447, updated on 6-Dec-2016
Official Symbol
IP6K2provided by HGNC
Official Full Name
inositol hexakisphosphate kinase 2 provided by HGNC
Primary source
See related
Gene type
protein coding
RefSeq status
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
This gene encodes a protein that belongs to the inositol phosphokinase (IPK) family. This protein is likely responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4 and affect the growth suppressive and apoptotic activities of interferon-beta in some ovarian cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Tästä pyrofosfaattia tekevästä entsyymistä IP6K2 on useita artikkeleita.

Related articles in PubMed

  1. Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. Nagata E, et al. J Biol Chem, 2005 Jan 14. PMID 15533939
  2. Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. Morrison BH, et al. J Biol Chem, 2001 Jul 6. PMID 11337497, Free PMC Article
See all (33) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. IHPK2 over expression enhances sensitivity of ovarian carcinoma cells to radiation, IFN-beta, caspase 8 and DR4

Muistiin inositolihexakisfosfaattikinaasista
24.1. 2016

IPP-syntaasi 1 (PPIP5K1 geeni)

PPIP5K1 geeni, kromosomi 15q15.3

Synonyyminimet: HISPPD2A ( histidiinihappofosfataasidomaanin sisältävä proteiini 2A )
IP6K-perhe, IP6-kinaasiperhe
IPS1, inositol pyrophosphate synthase 1 , IPP syntaasi 1
Tämä proteiini omaa kaksoisfunktion ( dual functional inositolkinase)
Ensin se fosforyloi IP6- muodon PP-IP5 muotoon., siis IP7-muotoon.
Sitten se fosforyloi PP-IP5- muodon (PP)2-IP4 muotoon, siis IP8 muotoon. 
Geenituoteta aktivoi solun  hyperosmoottinen stressi. 

PPIP5K1 diphosphoinositol pentakisphosphate kinase 1 [ Homo sapiens (human) ]

Gene ID: 9677, updated on 19-Jan-2017
Official Symbol
PPIP5K1provided by HGNC
Official Full Name
diphosphoinositol pentakisphosphate kinase 1provided by HGNC
Primary source
See related
Ensembl:ENSG00000168781 MIM:610979; Vega:OTTHUMG00000059758
Gene type
protein coding
RefSeq status
Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
This gene encodes a dual functional inositol kinase. The encoded enzyme converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate and diphosphoinositol pentakisphosphate to bis-diphosphoinositol tetrakisphosphate. This protein may be important for intracellular signaling pathways. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 15.[provided by RefSeq, Jun 2010

Tästä on muutamia uusia artikkeleita:

Related articles in PubMed

  1. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. Fridy PC, et al. J Biol Chem, 2007 Oct 19. PMID 17690096
See all (16) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. Upon activation of the appropriate cell-surface receptors to stimulate PtdIns(3,4,5)P3 synthesis, human PPIP5K1 translocates from the cytoplasm to the plasma membrane.
Muistiin 24.1. 2017

p53 välitteinen apoptoosi tarvitsee IP6K2 entsyymiä

 IP6K2 sitoutuu suoraan p53 proteiiniin.
 LÄHDE:  p53-mediated apoptosis requires inositol hexakisphosphate kinase-2

Inositol pyrophosphates have been implicated in numerous biological processes. Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), influences apoptotic cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a transcriptional program leading to cell-cycle arrest or apoptosis

We demonstrate that IP6K2 is required for p53-mediated apoptosis and modulates the outcome of the p53 response. Gene disruption of IP6K2 in colorectal cancer cells selectively impairs p53-mediated apoptosis, instead favoring cell-cycle arrest. IP6K2 acts by binding directly to p53 and decreasing expression of proarrest gene targets such as the cyclin-dependent kinase inhibitor p21.

Among the inositol phosphates, inositol 1,4,5-trisphosphate is best known for its release of intracellular calcium (1). The inositol pyrophosphates (IPPs), synthesized by inositol hexakisphosphate kinases (IP6Ks), regulate numerous processes including chemotaxis (2), telomere length (3, 4), endocytic trafficking (5), exocytosis (6), and apoptosis (7, 8).

 The principal inositol pyrophosphate, diphosphoinositol pentakisphosphate (5-PP-IP5), here designated IP7, is generated by three IP6 kinases that are the products of three separate genes (9).

 Another isomer of IP7, 3-PP-IP5, is synthesized by a distinct enzyme, Vip1, and regulates cell shape, growth, and phosphate disposition of yeast (10, 11).
 IP6K1 has been directly implicated in vesicular trafficking and tissue growth, because IP6K1-deleted mice manifest diminished insulin release, slowed growth, and defects in spermiogenesis (12). IP6K2 selectively impacts cell death, because its overexpression sensitizes cells to diverse apoptotic stimuli such as DNA damage, hypoxia, hydrogen peroxide, and interferon-β; knockdown of IP6K2 but not IP6K1 or IP6K3 diminishes sensitivity to such stimuli (7, 8, 13, 14).

 Recently, Lindner and coworkers (15) developed IP6K2 knockout mice that are predisposed to invasive aerodigestive tract carcinoma driven by chemical carcinogenesis, and fibroblasts from the mice resist γ-irradiation. The mechanism by which IP6K2 regulates cell death has not been established. 

We now show that IP6K2 is required for p53-mediated apoptosis and acts by binding p53 and selectively diminishing expression of its pro-cell-cycle arrest targets.

måndag 23 januari 2017

Lisätietoja saatu kalvodynamiikasta ja solusignaloinnista

Organelle Crosstalk in Membrane Dynamics and Cell Signalling
New molecular mechanisms of inter-organelle lipid transport
Guillaume Drin, Joachim Moser von Filseck, Alenka Čopič
Biochemical Society Transactions Apr 11, 2016, 44 (2) 486-492; DOI: 10.1042/BST20150265
 LIPIDIT ovat tarkalleen asettautuneina solukalvoissa ja niihin liittyy  organellispesifisiä  proteiineja. Tiedetään,että  pääasiallinen solulipidien tehdas  on endoplasminen retikulum  eli ER verkosto.  Täten onkin avainasemassa olevaa tietoa, miten eri lipidit sitten jakautuvat eri aitioihinsa rakkulakuljetuksella tai nonvesikulaarista tietä. Nykyään koetetaan ratkaista, miten lipideitä kuljettavat proteiinit (LTP) toimivat - joko  kuljettamalla pitkiä matkoja tai keskittyen kalvokontaktikohtiin (MCS), joissa kaksi organellia ovat lähellä toisiaan.

  • Abstract
  • Lipids are precisely distributed in cell membranes, along with associated proteins defining organelle identity. Because the major cellular lipid factory is the endoplasmic reticulum (ER), a key issue is to understand how various lipids are subsequently delivered to other compartments by vesicular and non-vesicular transport pathways.
  •  Efforts are currently made to decipher how lipid transfer proteins (LTPs) work either across long distances or confined to membrane contact sites (MCSs) where two organelles are at close proximity. 
Nykyistä tietoa  (ORP) perheen proteiineista (oxysterolia sitovan proteiinin kaltaiset proteiinit)  on sekin, että ne eivät  kuljeta ja tunnista  vain steroleja vaan jotkut niistä voivat sitoa joko fosfatidyyli-inositoli 4-fosfaattia (PI-4P) ja sterolia tai PI-4P ja PS ( fosfatidyyliseriiniä) sekä  vaihtaa näitä lipidejä keskenään ja täten käyttää fosfatidyyli-inositidien  (lipositolien) aineenvaihduntaa luomaan solulipidien gradienttia.
  • Recent findings reveal that proteins of the oxysterol-binding protein related-proteins (ORP)/oxysterol-binding homology (Osh) family are not all just sterol transporters/sensors: some can bind either phosphatidylinositol 4-phosphate (PtdIns(4)P) and sterol or PtdIns(4)P and phosphatidylserine (PS), exchange these lipids between membranes, and thereby use phosphoinositide metabolism to create cellular lipid gradients.
 Lipidien vaihto on todennäköisesti  laajalle levinnyt mekanismi , jota hyödyntää muutkin lipidien kuljettajaproteiinit  jakaen tehokkaasti lipidejä eri organellikalvojen  kesken.
 Lopuksi, kun nyt on löydetty enemmän sellaisia proteiineja, joilla on lipidiä sitova moduli (SMP tai STARTin kaltainen domeeni)  syntyy  uutta pohdintaa lipidien kuljetuksesta soluissa ja miten näiden  eri lipidikuljettajien aktiviteetit ovat koordinoidut.
  •  Lipid exchange is likely a widespread mechanism also utilized by other LTPs to efficiently trade lipids between organelle membranes.
  •  Finally, the discovery of more proteins bearing a lipid-binding module (SMP or START-like domain) raises new questions on how lipids are conveyed in cells and how the activities of different LTPs are coordinated.
DAG, diacylglycerol;
ER, endoplasmic reticulum;endoplasminen verkosto
FFAT, two phenylalanines in an acidic tract;
InsP3, inositol 1,4,5-triphosphate; inositoli-3P
LTP, lipid transfer protein; lipidinsiirtäjäproteiini
MCS, membrane contact site; kalvojen kontaktikohta
ORP, oxysterol-binding protein related-proteins; oxysterolia sitovan proteiinin kaltaiset proteiinit 
Osh, oxysterol-binding homology; oxysterolia sitovaa  homologia
PA, phosphatidic acid;fosfatidihappo, PtdOH  on toinen lyhennys
PH, pleckstrin homology; plekstriinihomologiaa
PtdIns(4, 5)P2, phosphatidylinositol 4,5-bisphosphate; PIP2, tai PtdIns-P2
PtdIns(4)P, phosphatidylinositol 4-phosphate;PI4P tai PtdIns-(4)P
PtdIns, phosphatidylinositol; PI  (lipositoli)
PM, plasma membrane;plasmakalvo
PS, phosphatidylserine;PtdSer, Fosfatidyyliseriini
SMP, synaptotagmin-like, mitochondrial and lipid-binding protein;
START, StAR-related lipid transfer;
TMD, transmembrane domain, transmembraaninen domaani

PI -PthOH kierto PM-ER vyöhyke, Nir2-kuljettajaproteiini , ALS

Biochem Soc Trans. 2016 Feb;44(1):197-201. doi: 10.1042/BST20150187.

Phosphatidylinositol  (PI)  and phosphatidic acid (PA) transport between the ER and plasma membrane during PLC activation requires the Nir2 protein.

Tiivistelmä  Suomennettu 24.6. 2017


Rajoittuneen  plasmamebraanilipidi PIP2- altaan PLC- välitteinen hydrolyysi vaatii täydentämistä laajasta PI altaasta ja siinä toimii kinaasit PI4-K- ja PI4P-5K.
Koska PI molekyylit syntetisoituvat endoplasmisessa retikulumissa (ER)  ja PIP2 generoituu plasmakalvossa, on oletettu, että  PI molekyyliä siirtävät proteiinit (PITP) antavat keinon tämän lipidin siirtämisfunktioon.   Tuoreet tutkimukset ovat tunnsitaneet PITP-proteiinin Nir2 olevan tärkeä PI- molekyylin kuljettamiseksi endoplasmiseseta retikulumista  plasmakalvoon.havaittiin myös , että Nir2 proteiini vaaditaan kuljetatmaan  fosfatidihappoa PtdOH  plasmakalvosta endoplasmiseen retikulumiin.   Nämä löydöt  ovat valottaneet PI ja PAmolekyylien  ei-vesikulaarista  kuljetusta  ER-P; kontaktivyöhykkeessä, josta on mahdollinen linkkiytyminen hyvin tuhoisiin ihmistauteihin.

Jos Nir2-kuljettajaproteiini puuttuu soluista ,PLC-aktivaatio johtaa  fosfatidaatin (PtdOH) kertymiseen plasmakalvoon ja PI-synteesi vaikeutuu vakavasti.
Lepäävissä soluissa Nir2 lokalisoituu endoplasmiseen verkostoon tekemällä interaktion FFAT domaaniin  ER-sitoutuneissa VAMP-assosioituneissa proteiineissa  VAP-A ja VAP-B. 
Kun PLC on  aktivoitunut, Bir2 myös sitoutuu plasmakalvoon tekemällä interaktion  C-terminaaliseslla domaanillaan DAG (diasyyliglyseroli)  ja  PA  (fosfatidyylihappo) molekyyleihin. Näiden interaktioitten välityksellä  Nir2  toimii ER- PM ( endoplasmisen retikulumin ja plasmakalvon)  kontaktivyöhykkeinä  
VAP-B mutaatiot joita on tunnsitettu amyotroofisessa lateraaliskleroosissa (ALS)  eli Lou-Gehrigin taudissa , aiheuttavat VAP-B-proteiinin aggrekaatioita, jotka sitten haittaavat sitoutumalla useisiin proteiineihin joihin kuuluu Nir2.
  • Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] requires replenishment from a larger pool of phosphatidylinositol (PtdIns) via sequential phosphorylation by PtdIns 4-kinases and phosphatidylinositol 4-phosphate (PtdIns4P) 5-kinases.
  •  Since PtdIns is synthesized in the endoplasmic reticulum (ER) and PtdIns(4,5)P2 is generated in the PM, it has been postulated that PtdIns transfer proteins (PITPs) provide the means for this lipid transfer function.   Recent studies identified the large PITP protein, Nir2 as important for PtdIns transfer from the ER to the PM.   It was also found that Nir2 was required for the transfer of phosphatidic acid (PtdOH) from the PM to the ER.
  •  In Nir2-depleted cells, activation of PLC leads to PtdOH accumulation in the PM and PtdIns synthesis becomes severely impaired.  In quiescent cells, Nir2 is localized to the ER via interaction of its FFAT domain with ER-bound VAMP-associated proteins VAP-A and-B.
  •  After PLC activation, Nir2 also binds to the PM via interaction of its C-terminal domains with diacylglycerol (DAG) and PtdOH. Through these interactions, Nir2 functions in ER-PM contact zones.
  • Mutations in VAP-B that have been identified in familial forms of amyotrophic lateral sclerosis (ALS or Lou-Gehrig's disease) cause aggregation of the VAP-B protein, which then impairs its binding to several proteins, including Nir2.
  •   These findings have shed new lights on the importance of non-vesicular lipid transfer of PtdIns and PtdOH in ER-PM contact zones with a possible link to a devastating human disease.


amyotrophic lateral sclerosis; endoplasmic reticulum; lipid transfer; phosphatidyl-inositol; phospholipase C

Fosfatidaattifosforylaasi PAP1 ja lipidifosfaattifosforylaasi PAP2 (LPP)
The Kennery Pathway for the biosynthesis of Phospholipids and triglycerides. 

Geeni PLPP1, kromosomi 5q11.2.  PAP-perheen   entsyymi  Phospholipide phosphatase 1, muuttaa fosfatidaatin  DAG;ksi, jok amenee glyserolipidisynteesiin ja vaikuttaa PLD- välitteisessä signaalin kuljetuksessa.
Nimet: LLP1a, LPP1, PAP-2a, PAP2, PPAP2a. osllistuu  lipidien hydrolyysiin ja soluun ottoon solunuolkoisesta tilasta. Säätelyllä on merkitystä myös jossain ihmissyövässä ( ovario ca) . Allaolevasta lätheestä enemmän tietoa.

Geeni PLPP3,  PAP-perheen entsyymi  Phospholipidi phosphatase3
Kromosomi 1p32.2.
Synonyymiset nimet:  Dn42, LPP3, PAP2B, PPAP2B, VCIP
Hydrolysoi extrasellulaarisia lysofosfatidaatteja ja lyhytketjuisia  fosfatidihappoja. EGF lisää sen expressiota.
Paljon tutkimusta sfingomyeliinin metabolian alalta löytyy lähteestä. erityisalue: 
keuhkoissa toimii LPP- tyyppisen mebraanisen  fosfataasin lisäksi sytosolinen  magnesiumista riippuvainen fosfatidaatin fosfohydrolaasi "PAP1" ( jonka geeniä nyt kuitenkaan en löydä erikseen PubMedista; asiassa on jotakin  vielä taxonomista) .   Keuhkolesitiinin runsaassa ja riittävässä  tuotossa  näitä tarvitaan.

Geeni PLPP2 , PAP- perheen entsyymi , Phospholipide phosphatase-2. Synonyymejä LPP2, PAP-2c, PAP2-g, PPAP2C. Tämä geeni löytyi 1998.
Kromosomi 19p13.3.  Näillä on kalvoon assosioituvaa PAP-aktiivisututa. Tämä  säätelee S-faasiin  menoa solusyklissä  koeäeläinfibroblastissa. Tämän expressio on erilaista normaalissa ja tuumorikudoksessa.