Reticulon 4 Is Necessary for Endoplasmic Reticulum Tubulation, STIM1-Orai1 Coupling, and Store-operated Calcium Entry

2016

Trends in Cell Biology

105

In eukaryotic cells, the endoplasmic reticulum (ER) is constructed as a network of tubules and sheets that exist in one continuous membrane system. Several classes of integral membrane protein have been shown to shape ER membranes. Functional studies using mutant proteins have begun to reveal the significance of ER morphology and membrane dynamics. In this review, we discuss the common protein modules and mechanisms that generate the characteristic shape of the ER. We also describe the cellular functions closely related to ER morphology, particularly contacts with other membrane systems, and their potential roles in the development of multicellular organisms.

Section: Er-pm Contact Sitesmentioning

confidence: 99%

Shaping the Endoplasmic Reticulum into a Social Network

2016

Trends in Cell Biology

105

“…Although the underlying mechanisms of aberrant angiogenesis in PDR is less than completely understood, lines of evidence shows that hyperglycemia is the most influential factor that contributes to the angiogenesis [34, 35]. Nogo-B, one of the evolutionary conservative proteins of endoplasmic reticulum that primarily play a role in promoting membrane curvature and tubules maintenance, was reported as a regulator of vascular remodeling and blood pressure, suggesting its role in vasvluar function [21, 22, 36, 37]. However, the role and function of Nogo-B in angiogenesis, especially in PDR have not been established yet.…”

Section: Discussionmentioning

confidence: 99%

Nogo-B Promotes Angiogenesis in Proliferative Diabetic Retinopathy via VEGF/PI3K/Akt Pathway in an Autocrine Manner

Wang

et al. 2017

Cell Physiol Biochem

Background/Aims: Nogo-B, a conservative protein of endoplasmic reticulum, is a member of the reticulon family of proteins. Proliferative diabetic retinopathy (PDR) is the major concerning problem of diabetic retinopathy. This study explored the role of Nogo-B in the regulation of angiogenesis in PDR patients and primary human retinal endothelial cells (HRMECs). Methods: Nogo-B was down-regulated through the use of Lentivirus-NogoB-RNAi, the effects of Nogo-B on angiogenesis under high glucose stimulation were evaluated via CCK-8 assay, wound closure assay, transwell assay, and tube formation assay. Expression of Nogo-B, VEGF, PI3K and Akt were determined by western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA). Co-culture systerm was used to explore cell communication. Results: Nogo-B was highly enriched in ocular tissues of PDR patients and in HRMECs exposed to high glucose. Down-regulation of Nogo-B attenuated high glucose induced cell migration and tube formation in HRMECs. Mechanistically, in comparison with the negative control group, Lentivirus-NogoB-RNAi group had exhibited reduced VEGF secretion, weakened PI3K and Akt activation. Besides, high glucose treatment promoted the secretion of Nogo-B and presented as a “long-term memory”. Conclusions: These data collectively indicated that Nogo-B promoted angiogenesis in HRMECs via VEGF/PI3K/Akt pathway in an autocrine manner.

Journal of Cell Science

“…This connection is often associated with the management of Ca 2+ stores in the ER lumen. The ER protein STIM1 diffuses through the ER membrane to find binding partners in the plasma membrane including the Orai channel (Jozsef et al, 2014;Soboloff et al, 2012). This set of proteinprotein associations works to restore ER Ca 2+ through the storeoperated Ca 2+ channel system.…”

Section: Introductionmentioning

confidence: 99%

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Summerville

Faust

Fan

et al. 2016

108

Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.