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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.


ESCRT system in mammalian cells. ESCRT-associated membrane deformation and abscission machinery works in a versatile phenomenon at particular sites in the cell as indicated by red boxes. VPS, vacuolar protein sorting; MVB, multivesicular body.
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ijms-17-01401-f005: ESCRT system in mammalian cells. ESCRT-associated membrane deformation and abscission machinery works in a versatile phenomenon at particular sites in the cell as indicated by red boxes. VPS, vacuolar protein sorting; MVB, multivesicular body.

Mentions: Endocytosed ubiquitinated membrane proteins, which are destined for lysosomal degradation, are recruited to a specialized area on endosomal membranes by multiprotein complexes named ESCRT-0, -I and -II. Sequentially transferred cargoes are further transported into inward budding vesicles by concomitant membrane deformation with spirally polymeric ESCRT-III [10]. Disassembly of the ESCRT complexes by the AAA-type ATPase VPS4 pinches off the buds into multivesicular bodies (MVBs). This ESCRT system in MVB sorting is conserved from yeast to humans [10], but remodeled machineries consisting of ESCRT-III/VPS4 as well as parts of the complexes and accessories are used in different combinations for exerting specific functions, such as virus budding, cytokinetic final abscission of daughter cells at the midbody, extracellular vesicle release, plasma membrane repair, neuron pruning, nuclear pore complex (NPC) surveillance, and nuclear envelope (NE) reformation (Figure 5) (see Refs. [10,11] for reviews and references therein). ALG-2 has been shown to be involved only in the following two ESCRT systems, but involvement in other systems is not necessarily excluded.


Multifaceted Roles of ALG-2 in Ca 2+ -Regulated Membrane Trafficking
ESCRT system in mammalian cells. ESCRT-associated membrane deformation and abscission machinery works in a versatile phenomenon at particular sites in the cell as indicated by red boxes. VPS, vacuolar protein sorting; MVB, multivesicular body.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01401-f005: ESCRT system in mammalian cells. ESCRT-associated membrane deformation and abscission machinery works in a versatile phenomenon at particular sites in the cell as indicated by red boxes. VPS, vacuolar protein sorting; MVB, multivesicular body.
Mentions: Endocytosed ubiquitinated membrane proteins, which are destined for lysosomal degradation, are recruited to a specialized area on endosomal membranes by multiprotein complexes named ESCRT-0, -I and -II. Sequentially transferred cargoes are further transported into inward budding vesicles by concomitant membrane deformation with spirally polymeric ESCRT-III [10]. Disassembly of the ESCRT complexes by the AAA-type ATPase VPS4 pinches off the buds into multivesicular bodies (MVBs). This ESCRT system in MVB sorting is conserved from yeast to humans [10], but remodeled machineries consisting of ESCRT-III/VPS4 as well as parts of the complexes and accessories are used in different combinations for exerting specific functions, such as virus budding, cytokinetic final abscission of daughter cells at the midbody, extracellular vesicle release, plasma membrane repair, neuron pruning, nuclear pore complex (NPC) surveillance, and nuclear envelope (NE) reformation (Figure 5) (see Refs. [10,11] for reviews and references therein). ALG-2 has been shown to be involved only in the following two ESCRT systems, but involvement in other systems is not necessarily excluded.

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.