Välillä mieleen tullut ajatus: ER membraani, minkälainen se on.

Nyt kun kerään lista ERAD  proteiineista ja niiden  funktioista, täytyy palauttaa mieleen, että kaikki nämä tapahtumat  tapahtuvat jollain alustalla, telineellä, ja se on endoplasmisen retikulumin kalvo.  Sen normaaliudellakin on omia vaatimuksiaan. jos tekijt ja geenit ovat normaalit, saataa miljöötekijä kuten ravinto ja kertyvät  saasteet , rasvaliukoiset kehomyrkyt ja mikrobit vaikuttaa tähän telineeseen.

Otan muutaman tuoreen tiedon endoplasmisen retikulumin kalvosta.

(1)  https://www.ncbi.nlm.nih.gov/pubmed/29884707

J Lipid Res. 2018 Jun 8. pii: jlr.R085324. doi: 10.1194/jlr.R085324. [Epub ahead of print]

Lipid-transfer proteins rectify inter-organelle flux and accurately deliver lipids at membrane contact sites.

Hanada K¹. Abstract

The endoplasmic reticulum (ER) is the main center for the synthesis of various lipid types in cells, and newly synthesized lipids are delivered from the ER to other organelles. In the past decade, various lipid-transfer proteins (LTPs) have been recognized as mediators of lipid transport from the ER to other organelles; inter-organelle transport occurs at membrane contact sites (MCSs) and in a nonvesicular manner.
Although the intermembrane transfer reaction catalyzed by LTPs is an equilibrium reaction, various types of newly synthesized lipids are transported unidirectionally in cells. This review provides a brief history of the inter-organelle trafficking of lipids and summarizes the structural and biochemical characteristics of the ceramide transport protein CERT as a typical LTP acting at MCSs. In addition, this review compares several LTP-mediated inter-organelle lipid trafficking systems and proposes that LTPs generate unidirectional fluxes of specific lipids between different organelles by indirect coupling with the metabolic reactions that occur in specific organelles. Moreover, the available data also suggest that the major advantage of LTP-mediated lipid transport at MCSs may be the accuracy of delivery. Finally, how cholesterol is enriched in the plasma membrane is discussed from a thermodynamic perspective.  KEYWORDS:

CERT; Ceramides; Endoplasmic reticulum; Lipid transfer proteins; OSBP; Phospholipids/Trafficking; SMP; StARkin; Sterols; non-equilibrium thermodynamics

2.https://www.ncbi.nlm.nih.gov/pubmed/29782498

PLoS Biol. 2018 May 21;16(5):e2003864. doi: 10.1371/journal.pbio.2003864. eCollection 2018 May.

Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation.Quon E¹, Sere YY², Chauhan N², Johansen J¹, Sullivan DP², Dittman JS², Rice WJ³, Chan RB⁴, Di Paolo G^4,5, Beh CT^1,6, Menon AK².Abstract

Tether proteins attach the endoplasmic reticulum (ER) to other cellular membranes, thereby creating contact sites that are proposed to form platforms for regulating lipid homeostasis and facilitating non-vesicular lipid exchange. Sterols are synthesized in the ER and transported by non-vesicular mechanisms to the plasma membrane (PM), where they represent almost half of all PM lipids and contribute critically to the barrier function of the PM. To determine whether contact sites are important for both sterol exchange between the ER and PM and intermembrane regulation of lipid metabolism, we generated Δ-super-tether (Δ-s-tether) yeast cells that lack six previously identified tethering proteins (yeast extended synatotagmin [E-Syt], vesicle-associated membrane protein [VAMP]-associated protein [VAP], and TMEM16-anoctamin homologues) as well as the presumptive tether Ice2. Despite the lack of ER-PM contacts in these cells, ER-PM sterol exchange is robust, indicating that the sterol transport machinery is either absent from or not uniquely located at contact sites. Unexpectedly, we found that the transport of exogenously supplied sterol to the ER occurs more slowly in Δ-s-tether cells than in wild-type (WT) cells. We pinpointed this defect to changes in sterol organization and transbilayer movement within the PM bilayer caused by phospholipid dysregulation, evinced by changes in the abundance and organization of PM lipids. Indeed, deletion of either OSH4, which encodes a sterol/phosphatidylinositol-4-phosphate (PI4P) exchange protein, or SAC1, which encodes a PI4P phosphatase, caused synthetic lethality in Δ-s-tether cells due to disruptions in redundant PI4P and phospholipid regulatory pathways. The growth defect of Δ-s-tether cells was rescued with an artificial "ER-PM staple," a tether assembled from unrelated non-yeast protein domains, indicating that endogenous tether proteins have nonspecific bridging functions. Finally, we discovered that sterols play a role in regulating ER-PM contact site formation. In sterol-depleted cells, levels of the yeast E-Syt tether Tcb3 were induced and ER-PM contact increased dramatically. These results support a model in which ER-PM contact sites provide a nexus for coordinating the complex interrelationship between sterols, sphingolipids, and phospholipids that maintain PM composition and integrity.

(3) https://www.ncbi.nlm.nih.gov/pubmed/29526591

Curr Biol. 2018 Mar 19;28(6):915-926.e9. doi: 10.1016/j.cub.2018.02.020. Epub 2018 Mar 8.

Architecture of Lipid Droplets in Endoplasmic Reticulum Is Determined by Phospholipid Intrinsic Curvature. Choudhary V¹, Golani G², Joshi AS¹, Cottier S³, Schneiter R³, Prinz WA⁴, Kozlov MM⁵. Abstract

Lipid droplets (LDs) store fats and play critical roles in lipid and energy homeostasis. They form between the leaflets of the endoplasmic reticulum (ER) membrane and consist of a neutral lipid core wrapped in a phospholipid monolayer with proteins. Two types of ER-LD architecture are thought to exist and be essential for LD functioning. Maturing LDs either emerge from the ER into the cytoplasm, remaining attached to the ER by a narrow membrane neck, or stay embedded in the ER and are surrounded by ER membrane.
 Here, we identify a lipid-based mechanism that controls which of these two architectures is favored. Theoretical modeling indicated that the intrinsic molecular curvatures of ER phospholipids can determine whether LDs remain embedded in or emerge from the ER; lipids with negative intrinsic curvature such as diacylglycerol (DAG) and phosphatidylethanolamine favor LD embedding, while those with positive intrinsic curvature, like lysolipids, support LD emergence. This prediction was verified by altering the lipid composition of the ER in S. cerevisiae using mutants and the addition of exogenous lipids. We found that fat-storage-inducing transmembrane protein 2 (FIT2) homologs become enriched at sites of LD generation when biogenesis is induced. DAG accumulates at sites of LD biogenesis, and FIT2 proteins may promote LD emergence from the ER by reducing DAG levels at these sites. Altogether, our findings suggest that cells regulate LD integration in the ER by modulating ER lipid composition, particularly at sites of LD biogenesis and that FIT2 proteins may play a central role in this process. KEYWORDS:

diacylglycerol; endoplasmic reticulum; fat-storage-inducing transmembrane protein; lipid droplets; lysolipids; membrane binding energy; membrane curvature; phospholipid intrinsic curvature

Missä kohtaa solussa sijaitsee Endoplasminen retikulum, ER,  endoplasminen verkosto? Mielestäni hyvä optusvideo on tässä linkissä.  Siinä on solu, solun sisällä tuma, punaisella värillä endoplasminen verkosto ja sen vieressä Golgin apparaatti.

https://www.youtube.com/watch?v=QO4WwyVt3cU

Endoplasmisessa verkostossa ribosomit kirjoittavat aminohappoketjuiksi solutumasta tulleen koodin mRNA koodin ja sitten ER ja Golgin laite yhdessä toimittavat  vasta syntetisoidun  peptidin  muokkauksen  valmiiksi- niitä on  proteiineja tuhansittain.  Osa endoplamsista verkostoa huolehtii myös rasva-aineittein lipidien tuotannosta.   Samalla   tuotetaan myös  " talon seinät" eli  ER:n tarvitsemat omat  rakennemolekyylit ja funktionaaliset molekylit, jotka jäävät pysytelemään paikallisina. .  Monenlaisia koneistoja toimii  asettuneina näihin  ER- kalvoihin ja niillä on  selvät integraatio- ja tehtäväalueensa.
Niitä on esim ERQC, proteiinin kvaliteettikontrolli,  vaste laskostumattomaan proteiiniin  eli  UPR ja  laskostumattoman ja  viallisen proteiinin hajoitus ERAD.   Suuri tehtävä on tuhansien  normaaliproteinien tuottaminen  ja sen ohella  viallisten  arviointi, korjausyritys ja siirto normaalien joukkoon   eritystielle tai sitten hajoitus.

(Olen  lukemassa sitä ERAD osaa ja siihen koneistoon kuuluvia jäseniä)

https://www.sciencedirect.com/science/article/pii/S0014579306003656