dGRASP-Mediated Noncanonical Integrin Secretion Is Required for Drosophila Epithelial Remodeling

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.
Developmental Cell (Impact Factor: 9.71). 03/2008; 14(2):171-82. DOI: 10.1016/j.devcel.2007.12.006
Source: PubMed


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.


Available from: Catherine Rabouille
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    • "FGF2 is assembled into oligomers by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ), which is then suggested to be translocated across the plasma membrane through a lipidic pore (Steringer et al, 2012). The delivery of aPS1 integrin from the ER to the plasma membrane in Drosophila at a specific early developmental stage is also reported to bypass the Golgi membrane and requires the Drosophila GRASP orthologue dGRASP (Schotman et al, 2008). However, little else is known about the requirement for the trafficking of the aPS1 integrin. "
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    • "As a plasma membrane protein, GRASP could also act as a tether for endosomal or lysosomal compartments that have engulfed cytoplasmic AcbA in exosomes, or to which AcbA had been delivered by an autophagy-like process [165]. This cellular distribution and related functions would be in agreement with the observation that, during D. melanogaster development, GRASP is required for the delivery of α-integrin to the plasma membrane through a Golgi-independent manner [166]. Although most of these hypotheses still require experimental proof, a realistic perspective is that GRASP might be required for the vesicular traffic of a number of molecules in eukaryotic cells. "
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    • "The small GTPase Rab8 has been implicated in cilia formation and appears to be required to deliver polycystin 2 to cilia (Hoffmeister et al., 2011). GRASP protein family members (Vinke et al., 2011) were shown to participate to the mechanism that underlies the Golgi bypass of aPS1 in Drosophila (Schotman et al., 2008) and that of CFTR in HeLa cells (Gee et al., 2011). It seems that under conditions that prevent normal exit of CFTR from the ER, GRASP55 binds the last four C-terminal amino-acid residues of CFTR through its PDZ1 domain, thereby mediating its exit from the ER followed by transport to the plasma membrane in a Golgi-independent manner (Gee et al., 2011). "

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