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.

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    • "At the same stages, dGRASP is needed for αPS1 exit from the ER, suggesting that dGRASP somehow mediates its packaging into vesicles and/or the tethering of these vesicles to specific plasma membrane domains (Figure 2B). This is supported by the finding that dGRASP mRNA is enriched near these plasma membrane domains, likely leading to its local synthesis (Schotman et al., 2008). Interestingly, the targeted localization of dGRASP mRNA near the plasma membrane is triggered by mechanical stress (Schotman et al., 2009; Giuliani et al., 2014), suggesting that this might be the trigger for the integrin subunit Golgi bypass. "
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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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