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Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking

View Article: PubMed Central - PubMed

ABSTRACT

ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.

No MeSH data available.


Subnetwork of ALG-2 and interacting proteins in the COPII system. Ca2+-dependent physical links with ALG-2 are indicated by double-headed arrows colored in red. Only two pairs of the Sec31A/Sec13 complex in the COPII outer shell are shown for simplicity. Conversion of the ALG-2 dimer and ALG-2/peflin heterodimer may occur in the cell.
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ijms-17-01401-f007: Subnetwork of ALG-2 and interacting proteins in the COPII system. Ca2+-dependent physical links with ALG-2 are indicated by double-headed arrows colored in red. Only two pairs of the Sec31A/Sec13 complex in the COPII outer shell are shown for simplicity. Conversion of the ALG-2 dimer and ALG-2/peflin heterodimer may occur in the cell.

Mentions: A subset of annexin A11 (AnxA11) colocalizes with Sec31A and ALG-2 at the ERES [94]. Physical association of AnxA11 with Sec31A is mediated by dimeric ALG-2 that bridges AnxA11 and Sec31A by functioning as a Ca2+-dependent adaptor as in the case of ALIX–ESCRT-I interaction [34,35]. This adaptor function seems specific in selecting partners because ALG-2 did not bridge ALIX and Sec31A [94]. Knockdown of either AnxA11 or ALG-2 accelerated ER-to-Golgi transport of VSV-G in HT1080 cells [94]. AnxA11 may function as a Ca2+-dependent membrane anchor to hold the COPII vesicles at the ERES until abscission is ready (Figure 7). It is possible that unknown membrane-tethering proteins associating with ALG-2 also regulate the rate of budding and abscission process.


Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking
Subnetwork of ALG-2 and interacting proteins in the COPII system. Ca2+-dependent physical links with ALG-2 are indicated by double-headed arrows colored in red. Only two pairs of the Sec31A/Sec13 complex in the COPII outer shell are shown for simplicity. Conversion of the ALG-2 dimer and ALG-2/peflin heterodimer may occur in the cell.
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Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037681&req=5

ijms-17-01401-f007: Subnetwork of ALG-2 and interacting proteins in the COPII system. Ca2+-dependent physical links with ALG-2 are indicated by double-headed arrows colored in red. Only two pairs of the Sec31A/Sec13 complex in the COPII outer shell are shown for simplicity. Conversion of the ALG-2 dimer and ALG-2/peflin heterodimer may occur in the cell.
Mentions: A subset of annexin A11 (AnxA11) colocalizes with Sec31A and ALG-2 at the ERES [94]. Physical association of AnxA11 with Sec31A is mediated by dimeric ALG-2 that bridges AnxA11 and Sec31A by functioning as a Ca2+-dependent adaptor as in the case of ALIX–ESCRT-I interaction [34,35]. This adaptor function seems specific in selecting partners because ALG-2 did not bridge ALIX and Sec31A [94]. Knockdown of either AnxA11 or ALG-2 accelerated ER-to-Golgi transport of VSV-G in HT1080 cells [94]. AnxA11 may function as a Ca2+-dependent membrane anchor to hold the COPII vesicles at the ERES until abscission is ready (Figure 7). It is possible that unknown membrane-tethering proteins associating with ALG-2 also regulate the rate of budding and abscission process.

View Article: PubMed Central - PubMed

ABSTRACT

ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.

No MeSH data available.