Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

Helm, Jared R.; Bentley, Marvin; Thorsen, Kevin; Wang, Ting; Foltz, Lauren; Oorschot, Viola; Klumperman, Judith; Hay, Jesse

doi:10.1074/jbc.m114.561829

Cited by 43 publications

(67 citation statements)

References 75 publications

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“…In contrast, co-expression of the minor isoform of ALG-2, ALG-2 ⌬GF122 that binds Sec31A but lacks the adaptor function to bridge AnxA11 and Sec31A (Fig. 3C), fails to inhibit transport (54). This implies that AnxA11 may be involved in the inhibitory effect of the complex between ALG-2 and the Pro-rich region of Sec31A in ER-to-Golgi transport.…”

Section: Discussionmentioning

confidence: 57%

“…The acceleration of tsO45-G-GFP transport in the ALG-2 knockdown cells is in good agreement with results obtained from the in vitro studies. More recently (after submission of this study), Helm et al (54) reported that exogenous co-expression of the major isoform of ALG-2 and the Pro-rich region of Sec31A inhibits ER-to-Golgi transport of tsO45-G-GFP in normal rat kidney cells. In contrast, co-expression of the minor isoform of ALG-2, ALG-2 ⌬GF122 that binds Sec31A but lacks the adaptor function to bridge AnxA11 and Sec31A (Fig.…”

Section: Discussionmentioning

confidence: 99%

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A New Role for Annexin A11 in the Early Secretory Pathway via Stabilizing Sec31A Protein at the Endoplasmic Reticulum Exit Sites (ERES)

Shibata

Kanadome

Sugiura

et al. 2015

Journal of Biological Chemistry

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Background: Apoptosis-linked gene 2 (ALG-2) is a calcium-dependent adaptor protein that is recruited to the Sec31A-positive ERES. Results: Physical association between annexin A11 and Sec31A is mediated by ALG-2, and annexin A11 is required for stable association of Sec31A at the ERES. Conclusion: Annexin A11 participates in ER-to-Golgi trafficking. Significance: Annexin A11 is the first annexin shown to modulate the early secretory pathway.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

A New Role for Annexin A11 in the Early Secretory Pathway via Stabilizing Sec31A Protein at the Endoplasmic Reticulum Exit Sites (ERES)

Shibata

Kanadome

Sugiura

et al. 2015

Journal of Biological Chemistry

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“…Interestingly, ALG-2 restricted HIV-1 production by disturbing Gag expression and membrane distribution. ALG-2 is involved in vesicular trafficking (35)(36)(37)(38)(39) via its interactions with ALIX and TSG101 and co-localization with VPS4B (14). Therefore, it is reasonable to speculate that ALG-2 might affect Gag trafficking within the cytosol.…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Study of Apoptosis-linked Gene-2·Heme-binding Protein 2 Interactions in HIV-1 Production

Zhang²,

Feng

et al. 2016

Journal of Biological Chemistry

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Edited by Dennis VoelkerIn the HIV-1 replication cycle, the endosomal sorting complex required for transport (ESCRT) machinery promotes viral budding and release in the late stages. In this process, the ESCRT proteins, ALIX and TSG101, are recruited through interactions with HIV-1 Gag p6. ALG-2, also known as PDCD6, interacts with both ALIX and TSG101 and bridges ESCRT-III and ESCRT-I. In this study, we show that ALG-2 affects HIV-1 production negatively at both the exogenous and endogenous levels. Through a yeast two-hybrid screen, we identified HEBP2 as the binding partner of ALG-2, and we solved the crystal structure of the ALG-2⅐HEBP2 complex. The function of ALG-2⅐HEBP2 complex in HIV-1 replication was further explored. ALG-2 inhibits HIV-1 production by affecting Gag expression and distribution, and HEBP2 might aid this process by tethering ALG-2 in the cytoplasm.The endosomal sorting complex required for transport (ESCRT) 3 machinery functions in HIV-1 budding and release in the late stages of viral replication (1-3). In this process, ALIX (ALG-2 interacting protein X) and TSG101 (tumor susceptibility gene 101), components of ESCRT-III and ESCRT-I, are recruited to the budding site of HIV-1 through interactions with HIV-1 Gag p6 (4 -8). This promotes the release of virion particles (9) with the help of AAA-ATPase VPS4B (vacuolar protein sorting 4 homolog B) (10, 11). The penta-EF-hand protein ALG-2 (apoptosis-linked gene-2, also known as PDCD6) participates in the process by interacting with both ALIX (12, 13) and TSG101 (14) in a calcium-dependent manner and bridges ESCRT-III and ESCRT-I through dimerization (15)(16)(17). However, the function of ALG-2 in viral replication, especially that of HIV-1, remains unknown.ALG-2 was first identified in a functional screen for anti-apoptotic proteins involved in T-cell receptor, Fas, and glucocorticoid-induced cell death (18). It was defined as a proapoptotic molecule because expression of its antisense strand led to rescue from cell death (19). However, ALG-2 knock-out mice are viable and exhibit normal T-cell development (20), which suggested that other redundant proteins might exist in mammalian cells. ALG-2 is a penta-EF-hand protein (13, 15), containing five repeats of the EF-hand motif, and coordinates three calcium ions via EF1, EF3, and EF5. However, the coordination of calcium by EF5 is weak and may be physiologically unimportant. ALG-2 exists as a dimer, which might be critical for its function as an adaptor molecule in signal transduction (15). ALG-2 can interact with dozens of proteins through several pockets (pockets 1-3) on its molecular surface. The binding motif for ALG-2, designated as the ALG-2-binding site (ABS), is a short sequence rich in Pro, Gly, and Tyr. Two typical ABS sequences have been described. ABS-1, which is represented as PPYPXXPGYP (X represents any residue) and occupies pocket 1 on the ALG-2 surface, is found in ALIX and PLSCR3 (6), whereas ABS-2, containing a PXPGF sequence that binds pocket 3, is found in SEC31 and PLSCR3 (1...

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“…Likewise, other protein factors could influence the shape of the forming COPII carrier by regulating the availability of inner or outer COPII proteins at ER exit sites. Candidates for such a function include the Sedlin component of the TRAPP complex (28), the ubiquitin ligase CUL3-KLHL12 (29), and Ca 2+ /ALG-2 (30,31), which binds to a site on Sec31 PRD that includes one of the two PPP motifs, residues 838 PPP 841 (32). The biochemical analysis and the mechanism that we have presented for TANGO1/cTAGE5 interplay with COPII should provide a basis on which to further explore the role of these protein factors in ER-to-Golgi transport.…”

Section: Discussionmentioning

confidence: 99%

TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats

Goldberg

2016

Proc. Natl. Acad. Sci. U.S.A.

159

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The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24•Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins. The affinity for Sec23 is concentrated in the proline-rich domains (PRDs) of TANGO1 and cTAGE5, but Sec23 recognizes merely a PPP motif. The PRDs contain repeated PPP motifs separated by proline-rich linkers, so a single TANGO1/cTAGE5 receptor can bind multiple copies of coat protein in a close-packed array. We propose that TANGO1/cTAGE5 promotes the accretion of inner coat proteins to the helical lattice. Furthermore, we show that PPP motifs in the outer coat protein Sec31 also bind to Sec23, suggesting that stepwise COPII coat assembly will ultimately displace TANGO1/cTAGE5 and compartmentalize its operation to the base of the growing COPII tubule.vesicle traffic | coat protein | procollagen T he coat protein complex II (COPII)-coated vesicles transport secretory and plasma membrane proteins from the endoplasmic reticulum (ER). COPII vesicle budding involves a stepwise assembly reaction: Membrane-bound Sar1-GTP recruits Sec23/24 to form the inner coat complex that, in turn, recruits the Sec13/31 outer coat protein (1). Sec13/31 self-assembles into a polyhedron, and in the process, it sculpts the ER membrane into a bud, producing a COPII-coated vesicle with a diameter of ∼60 nm (2-4).Small cargo molecules are captured during the budding reaction through mechanisms that are well established (5). However, the formation of canonical 60-nm COPII vesicles cannot explain the packaging of large cargos, such as the procollagen fibril with a length of 300-400 nm. Procollagen follows the conventional route of secretion taken by other extracellular proteins, and its ER export evidently depends on COPII carriers because mutations in genes encoding COPII proteins result in collagen secretion blockade, impaired extracellular matrix deposition, and abnormal craniofacial development (6-8). A key discovery was the identification of the receptor TANGO1 and its coreceptor cTAGE5 as ER-localized machinery for loading procollagen into COPII carriers (9, 10). TANGO1 has a luminal SH3 domain shown to interact with collagen VII and a cytosolic domain that interacts with Sec23/24. Both TANGO1 and cTAGE5 are required for collagen export from the ER (9, 10). The TANGO1 knockout mouse has generalized defects in extracellular matrix formation, owing to a block in ER export of multiple collagen types (11).Recent research has implicated post-ER membranes in TANGO1-mediated carrier formation (12, 13); however, the mechanism of action of TANGO1/cTAGE5 in procollagen export...

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Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

Cited by 43 publications

References 75 publications

A New Role for Annexin A11 in the Early Secretory Pathway via Stabilizing Sec31A Protein at the Endoplasmic Reticulum Exit Sites (ERES)

A New Role for Annexin A11 in the Early Secretory Pathway via Stabilizing Sec31A Protein at the Endoplasmic Reticulum Exit Sites (ERES)

Structural and Functional Study of Apoptosis-linked Gene-2·Heme-binding Protein 2 Interactions in HIV-1 Production

TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats

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