The SNARE Sec22b has a non-fusogenic function in plasma membrane expansion.
Development of the nervous system requires extensive axonal and dendritic growth during which neurons massively increase their surface area. Here we report that the endoplasmic reticulum (ER)-resident SNARE Sec22b has a conserved non-fusogenic function in plasma membrane expansion. Sec22b is closely apposed to the plasma membrane SNARE syntaxin1. Sec22b forms a trans-SNARE complex with syntaxin1 that does not include SNAP23/25/29, and does not mediate fusion. Insertion of a long rigid linker between the SNARE and transmembrane domains of Sec22b extends the distance between the ER and plasma membrane, and impairs neurite growth but not the secretion of VSV-G. In yeast, Sec22 interacts with lipid transfer proteins, and inhibition of Sec22 leads to defects in lipid metabolism at contact sites between the ER and plasma membrane. These results suggest that close apposition of the ER and plasma membrane mediated by Sec22 and plasma membrane syntaxins generates a non-fusogenic SNARE bridge contributing to plasma membrane expansion, probably through non-vesicular lipid transfer.
1] INSERM, U950, F-75013 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, ERL U950, F-75013 Paris, France [3] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France [4] Ecole des Neurosciences de Paris (ENP), F-75006 Paris, France [5].
Maja
M
Petkovic
1] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France [2] Membrane Dynamics and Intracellular Trafficking, Institute Jacques Monod, F-75013 Paris, France [3].
Aymen
A
Jemaiel
1] INSERM, U950, F-75013 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, ERL U950, F-75013 Paris, France [3] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France [4] Ecole Doctorale Frontières du Vivant (FdV) - Programme Bettencourt, Université Paris Descartes, Sorbonne Paris Cité, F-75004 Paris, France [5].
Frédéric
F
Daste
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Biologie Cellulaire de la Synapse, INSERM U1024, CNRS UMR8197, F-75005 Paris, France.
Christian G
CG
Specht
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Functional Imaging of Transcription, INSERM U1024, CNRS UMR8197, F-75005 Paris, France.
Ignacio
I
Izeddin
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Daniela
D
Vorkel
1] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France [2] Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Jean-Marc
JM
Verbavatz
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Functional Imaging of Transcription, INSERM U1024, CNRS UMR8197, F-75005 Paris, France.
Xavier
X
Darzacq
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Biologie Cellulaire de la Synapse, INSERM U1024, CNRS UMR8197, F-75005 Paris, France.
Antoine
A
Triller
Linda Crnic Institute for Down Syndrome and Department of Pediatrics, University Colorado School of Medicine, Aurora, Colorado 80045, USA.
Karl H
KH
Pfenninger
1] INSERM, U950, F-75013 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, ERL U950, F-75013 Paris, France [3] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France.
David
D
Tareste
1] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France [2] Membrane Dynamics and Intracellular Trafficking, Institute Jacques Monod, F-75013 Paris, France.
Catherine L
CL
Jackson
1] INSERM, U950, F-75013 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, ERL U950, F-75013 Paris, France [3] CNRS, UMR 7592, Institut Jacques Monod, F-75013 Paris, France.
Thierry
T
Galli
D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005865:Gestational Age; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D002352:Carrier Proteins; D050683:R-SNARE Proteins; C494212:STX1A protein, human; D029701:Saccharomyces cerevisiae Proteins; C106909:Sec22 protein, S cerevisiae; C572028:Sec22B protein, human; C432415:Sec22b protein, mouse; D050827:Syntaxin 1; C030363:lipid transfer protein