scholarly journals Role of the Sec22b–E-Syt complex in neurite growth and ramification

2020 ◽  
Vol 133 (18) ◽  
pp. jcs247148 ◽  
Author(s):  
Alessandra Gallo ◽  
Lydia Danglot ◽  
Francesca Giordano ◽  
Bailey Hewlett ◽  
Thomas Binz ◽  
...  
Keyword(s):  
Nervous System ◽  
Opposite Effect ◽  
Neurite Growth ◽  
Lipid Transfer ◽  
Wild Type ◽  
Lipid Transfer Proteins ◽  
Contact Sites ◽  
Developing Neurons ◽  
Clostridial Neurotoxin

ABSTRACTAxons and dendrites are long and often ramified neurites that need particularly intense plasma membrane (PM) expansion during the development of the nervous system. Neurite growth depends on non-fusogenic Sec22b–Stx1 SNARE complexes at endoplasmic reticulum (ER)–PM contacts. Here, we show that Sec22b interacts with members of the extended synaptotagmin (E-Syt) family of ER lipid transfer proteins (LTPs), and this interaction depends on the longin domain of Sec22b. Overexpression of E-Syts stabilizes Sec22b–Stx1 association, whereas silencing of E-Syts has the opposite effect. Overexpression of wild-type E-Syt2, but not mutants unable to transfer lipids or attach to the ER, increase the formation of axonal filopodia and ramification of neurites in developing neurons. This effect is inhibited by a clostridial neurotoxin cleaving Stx1, and expression of the Sec22b longin domain and a Sec22b mutant with an extended linker between the SNARE and transmembrane domains. We conclude that Sec22b–Stx1 ER–PM contact sites contribute to PM expansion by interacting with LTPs, such as E-Syts.This article has an associated First Person interview with the first author of the paper.

scholarly journals The interaction between non-fusogenic Sec22b-Stx complexes and Extended-Synaptotagmins promotes neurite growth and ramification

2019 ◽  
Author(s):  
Alessandra Gallo ◽  
Lydia Danglot ◽  
Francesca Giordano ◽  
Thomas Binz ◽  
Christian Vannier ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Opposite Effect ◽  
Neurite Growth ◽  
Lipid Transfer ◽  
Wild Type ◽  
Lipid Transfer Proteins ◽  
Contact Sites ◽  
Developing Neurons ◽  
Clostridial Neurotoxin

SummaryAxons and dendrites are long and often ramified neurites that need particularly intense plasma membrane (PM) expansion during the development of the nervous system. Neurite growth depends on non-fusogenic Sec22b–Stx1 SNARE complexes at endoplasmic reticulum (ER)-PM contacts. Here we show that Sec22b interacts with the endoplasmic reticulum lipid transfer proteins Extended-Synaptotagmins (E-Syts) and this interaction depends on the Longin domain of Sec22b. Overexpression of E-Syts stabilizes Sec22b-Stx1 association, whereas silencing of E-Syts has the opposite effect. Overexpression of wild-type E-Syt2, but not mutants unable to transfer lipids or attach to the ER, increase the formation of axonal filopodia and ramification of neurites in developing neurons. This effect is inhibited by a clostridial neurotoxin cleaving Stx1, expression of Sec22b Longin domain and a Sec22b mutant with extended linker between SNARE and transmembrane domains. We conclude that Sec22b-Stx1 ER-PM contact sites contribute to PM expansion by interacting with lipid transfer proteins such as E-Syts.

scholarly journals The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi contact sites

2019 ◽  
Author(s):  
Yuichi Wakana ◽  
Kaito Hayashi ◽  
Takumi Nemoto ◽  
Chiaki Watanabe ◽  
Masato Taoka ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Regulatory Protein ◽  
Cholesterol Transport ◽  
Lipid Transfer ◽  
Wild Type ◽  
Proteolytic Activation ◽  
Contact Sites ◽  
Transport Defect ◽  
Golgi Network

AbstractIn response to cholesterol deprivation, SCAP escorts SREBP transcription factors from the endoplasmic reticulum (ER) to the Golgi complex for their proteolytic activation, leading to gene expression for cholesterol synthesis and uptake. Here we show that in cholesterol-fed cells ER-localized SCAP interacts through Sac1 phosphoinositide 4-phosphate (PI4P) phosphatase with a VAP/OSBP complex, which mediates counter-transport of ER cholesterol and Golgi PI4P at ER-Golgi contact sites. SCAP knockdown inhibited the turnover of PI4P perhaps due to a cholesterol transport defect and altered the subcellular distribution of the VAP/OSBP complex. As in the case of perturbation of lipid transfer complexes at ER-Golgi contact sites, SCAP knockdown inhibited the biogenesis of the trans-Golgi network-derived transport carriers CARTS, which was reversed by expression of wild-type SCAP but not cholesterol sensing-defective mutants. Altogether, our findings reveal a new role of SCAP under cholesterol-fed conditions in the facilitation of CARTS biogenesis at ER-Golgi contact sites, depending on the ER cholesterol.SummarySCAP is the key regulatory protein in cholesterol metabolism. Wakana et al. describe a new role of SCAP in controlling Golgi PI4P turnover and the biogenesis of the Golgi-derived transport carries CARTS via cholesterol/PI4P exchange machinery at ER-Golgi contact sites.

Role of plant lipid transfer proteins in plant cell physiology—A concise review

Peptides ◽  
2007 ◽  
Vol 28 (5) ◽  
pp. 1144-1153 ◽  
Author(s):  
André de Oliveira Carvalho ◽  
Valdirene Moreira Gomes
Keyword(s):  
Plant Cell ◽  
Cell Physiology ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Plant Lipid ◽  
Concise Review

scholarly journals The Hob Proteins: Putative, Novel Lipid Transfer Proteins at ER-PM Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110523
Author(s):  
Sarah D. Neuman ◽  
Amy T. Cavanagh ◽  
Arash Bashirullah
Keyword(s):  
Structural Models ◽  
Model Systems ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Bona Fide ◽  
Membrane Contact ◽  
Mutant Cells ◽  
Critical Process

Nonvesicular transfer of lipids at membrane contact sites (MCS) has recently emerged as a critical process for cellular function. Lipid transfer proteins (LTPs) mediate this unique transport mechanism, and although several LTPs are known, the cellular complement of these proteins continues to expand. Our recent work has revealed the highly conserved but poorly characterized Hobbit/Hob proteins as novel, putative LTPs at endoplasmic reticulum-plasma membrane (ER-PM) contact sites. Using both S. cerevisiae and D. melanogaster model systems, we demonstrated that the Hob proteins localize to ER-PM contact sites via an N-terminal ER membrane anchor and conserved C-terminal sequences. These conserved C-terminal sequences bind to phosphoinositides (PIPs), and the distribution of PIPs is disrupted in hobbit mutant cells. Recently released structural models of the Hob proteins exhibit remarkable similarity to other bona fide LTPs, like VPS13A and ATG2, that function at MCS. Hobbit is required for viability in Drosophila, suggesting that the Hob proteins are essential genes that may mediate lipid transfer at MCS.

Role of glial cell-line derived neurotropic factor family receptor α2 in the actions of the glucagon-like peptides on the murine intestine

2007 ◽  
Vol 293 (2) ◽  
pp. G461-G468 ◽  
Author(s):  
Sean C. McDonagh ◽  
Jenny Lee ◽  
Angelo Izzo ◽  
Patricia L. Brubaker
Keyword(s):  
Nervous System ◽  
Substance P ◽  
Enteric Nervous System ◽  
Cell Line ◽  
Glial Cell ◽  
Wild Type ◽  
Intestinal Growth ◽  
Mrna Transcripts ◽  
Neurotropic Factor

The intestinal glucagon-like peptides GLP-1 and GLP-2 inhibit intestinal motility, whereas GLP-2 also stimulates growth of the intestinal mucosa. However, the mechanisms of action of these peptides in the intestine remain poorly characterized. To determine the role of the enteric nervous system in the actions of GLP-1 and GLP-2 on the intestine, the glial cell line-derived neurotropic factor family receptor α2 (GFRα2) knockout (KO) mouse was employed. The mice exhibited decreased cholinergic staining, as well as reduced mRNA transcripts for substance P-ergic excitatory motoneurons in the enteric nervous system (ENS) ( P < 0.05). Examination of parameters of intestinal growth (including small and large intestinal weight and small intestinal villus height, crypt depth, and crypt cell proliferation) demonstrated no differences between wild-type and KO mice in either basal or GLP-2-stimulated mucosal growth. Nonetheless, KO mice exhibited reduced numbers of synaptophysin-positive enteroendocrine cells ( P < 0.05), as well as a markedly impaired basal gastrointestinal (GI) transit rate ( P < 0.05). Furthermore, acute administration of GLP-1 and GLP-2 significantly inhibited transit rates in wild-type mice ( P < 0.05–0.01) but had no effect in GFRα2 KO mice. Despite these changes, expression of mRNA transcripts for the GLP receptors was not reduced in the ENS of KO animals, suggesting that GLP-1 and -2 modulate intestinal transit through enhancement of inhibitory input to cholinergic/substance P-ergic excitatory motoneurons. Together, these findings demonstrate a role for GFRα2-expressing enteric neurons in the downstream signaling of the glucagon-like peptides to inhibit GI motility, but not in intestinal growth.

The role of cAMP and its downstream targets in neurite growth in the adult nervous system

2017 ◽  
Vol 652 ◽  
pp. 56-63 ◽  
Author(s):  
Nicholas J. Batty ◽  
Keith K. Fenrich ◽  
Karim Fouad
Keyword(s):  
Nervous System ◽  
Neurite Growth ◽  
Downstream Targets
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