dGRASP-mediated noncanonical integrin secretion is required for Drosophila epithelial remodeling.
Integral plasma membrane proteins are typically transported in the secretory pathway from the endoplasmic reticulum and the Golgi complex. Here we show that at specific stages of Drosophila development corresponding to morphological changes in epithelia, apposed basolateral membranes separate slightly, allowing new plasma membrane contacts with basal extracellular matrix. At these sites, newly synthesized integrin alpha subunits are deposited via a mechanism that appears to bypass the Golgi. We show that the Drosophila Golgi resident protein dGRASP localizes to these membrane domains and that, in the absence of dGRASP, the integrin subunit is retained intracellularly in both follicular and wing epithelia that are found disrupted. We propose that this dGRASP-mediated noncanonical secretion route allows for developmental regulation of integrin function upon epithelial remodeling. We speculate that this mechanism might be used during development as a means of targeting a specific subset of transmembrane proteins to the plasma membrane.
Schotman
Hans
H
The Cell Microscopy Centre, Department of Cell Biology, Institute of Biomembranes, University Medical Centre Utrecht, AZU Room G02.525, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
Karhinen
Leena
L
Rabouille
Catherine
C
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D022001:Focal Adhesions / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D016023:Integrins / Q000096:biosynthesis / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D050765:Qa-SNARE Proteins; D034443:RNA Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism
D029721:Drosophila Proteins; C506558:GRASP65 protein, Drosophila; D000077614:Golgi Matrix Proteins; D016023:Integrins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger; D020126:Brefeldin A