Journal article

The Munc18-1 domain 3a loop is essential for neuroexocytosis but not for syntaxin-1A transport to the plasma membrane

Sally Martin, Vanesa M Tomatis, Andreas Papadopulos, Michelle P Christie, Nancy T Malintan, Rachel S Gormal, Shuzo Sugita, Jennifer L Martin, Brett M Collins, Frederic A Meunier

JOURNAL OF CELL SCIENCE | COMPANY OF BIOLOGISTS LTD | Published : 2013

Abstract

Munc18-1 plays a dual role in transporting syntaxin-1A (Sx1a) to the plasma membrane and regulating SNARE-mediated membrane fusion. As impairment of either function leads to a common exocytic defect, assigning specific roles for various Munc18-1 domains has proved difficult. Structural analyses predict that a loop region in Munc18-1 domain 3a could catalyse the conversion of Sx1a from a 'closed', fusion-incompetent to an 'open', fusion-competent conformation. As this conversion occurs at the plasma membrane, mutations in this loop could potentially separate the chaperone and exocytic functions of Munc18-1. Expression of a Munc18-1 deletion mutant lacking 17 residues of the domain 3a loop (Mu..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council Future Fellowship


Awarded by Australian Research Council LIEF grant


Funding Acknowledgements

This research was supported by a project grant from the National Health and Medical Research Council of Australia [grant number APP1044014 to F.A.M. and B.M.C.]; a Senior Research Fellowship from the National Health and Medical Research Council of Australia [grant number 569596 to F.A.M.]; an Australian Research Council Future Fellowship [grant number FT100100027 to B.M.C.]; and an Australian Research Council LIEF grant [grant number LE0882869 to F.A.M.].