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

Shibata, Hideki; Kanadome, Takashi; Sugiura, Hirofumi; Yokoyama, Takeru; Yamamuro, Minami; Moss, Stephen E.; Maki, Masatoshi

doi:10.1074/jbc.m114.592089

Cited by 44 publications

(68 citation statements)

References 54 publications

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“…DRP1 interacts with Annexin A6 62 . Annexin protein may maintain the architectural and functional features of ER exit sites 63 . Whether calcium regulation and annexins participate in DRP1 regulation of protein secretion and calcification requires further exploration.…”

Section: Discussionmentioning

confidence: 99%

Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress

Rogers

Maldonado

Hutcheson

et al. 2017

Circulation Research

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Rationale Mitochondrial changes occur during cell differentiation and cardiovascular disease. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. Objective To examine the effects of osteogenic promoting conditions on DRP1, and whether DRP1 inhibition alters the development of cardiovascular calcification. Methods and Results DRP1 was enriched in calcified regions of human carotid arteries, examined by immunohistochemistry. Osteogenic differentiation of primary human vascular smooth muscle cells (SMCs) increased DRP1 expression. DRP1 inhibition in human SMCs undergoing osteogenic differentiation attenuated matrix mineralization, cytoskeletal rearrangement, mitochondrial dysfunction, and reduced type 1 collagen secretion and alkaline phosphatase activity. DRP1 protein was observed in calcified human aortic valves, and DRP1 RNA interference reduced primary human valve interstitial cell calcification. Mice heterozygous for Drp1 deletion did not exhibit altered vascular pathology in a PCSK9 gain-of-function atherosclerosis model. However, when mineralization was induced via oxidative stress, DRP1 inhibition attenuated mouse and human SMC calcification. Femur bone density was unchanged in mice heterozygous for Drp1 deletion, and DRP1 inhibition attenuated oxidative stress-mediated dysfunction in human bone osteoblasts. Conclusions We demonstrate a new function of DRP1 in regulating collagen secretion and cardiovascular calcification, a novel area of exploration for the potential development of new therapies to modify cellular fibrocalcific response in cardiovascular diseases. Our data also support a role of mitochondrial dynamics in regulating oxidative stress-mediated arterial calcium accrual and bone loss.

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Section: Discussionmentioning

confidence: 99%

Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress

Rogers

Maldonado

Hutcheson

et al. 2017

Circulation Research

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“…We previously reported that ALG‐2 functions as a Ca 2+ ‐dependent adaptor protein mediating the indirect association between Sec31A and annexin A11 . Because both TFG and Sec31A localize at ERES, it is conceivable that ALG‐2 bridges the two proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Because there are at least four binding sites in an ALG‐2 homodimer, it is proposed that ALG‐2 functions as a Ca 2+ ‐dependent adaptor protein . We previously demonstrated that ALG‐2 bridges annexin A11 and Sec31A via the adaptor function and that annexin A11 is required for stabilization of Sec31A on the membranes of ERES . Because TFG binds to ALG‐2 with characteristics of ABM‐2‐containing proteins (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Rabbit polyclonal antibodies against Sec16A and Sec16B were kindly provided by the late K. Tani and Y. Maemoto (Tokyo University of Pharmacy and Life Science, Tokyo, Japan) . The following antibodies were raised as described previously: rabbit polyclonal antibody against ALG‐2 for western blotting , goat polyclonal antibody against ALG‐2 for immunostaining and rabbit polyclonal antibody against Sec31A for western blotting and immunostaining .…”

Section: Methodsmentioning

confidence: 99%

“…Outside the perinuclear area, TFG was detected at lower intensity as dot-like structures, many of which overlapped partially with the ALG-2/Sec31A-positive ones ( Fig observations suggest that TFG partially colocalized with ALG-2 at Sec31A-positive ERES. We previously reported that ALG-2 functions as a Ca 2+ -dependent adaptor protein mediating the indirect association between Sec31A and annexin A11 [23]. Because both TFG and Sec31A localize at ERES, it is conceivable that ALG-2 bridges the two proteins.…”

Section: Alg-2 Co-localizes With Tfg At Eresmentioning

confidence: 99%

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The calcium‐binding protein ALG‐2 promotes endoplasmic reticulum exit site localization and polymerization of Trk‐fused gene (TFG) protein

et al. 2016

Self Cite

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Apoptosis‐linked gene 2 (ALG‐2), which is a gene product of PDCD6, is a 22‐kDa Ca2+‐binding protein. Accumulating evidence points to a role for ALG‐2 as a Ca2+‐responsive adaptor protein. On binding to Ca2+, ALG‐2 undergoes a conformational change that facilitates its interaction with various proteins. It also forms a homodimer and heterodimer with peflin, a paralog of ALG‐2. However, the differences in cellular roles for the ALG‐2 homodimer and ALG‐2/peflin heterodimer are unclear. In the present study, we found that Trk‐fused gene (TFG) protein interacted with the ALG‐2 homodimer. Immunostaining analysis revealed that TFG and ALG‐2 partially overlapped at endoplasmic reticulum exit sites (ERES), a platform for COPII‐mediated protein transport from the endoplasmic reticulum. Time‐lapse live‐cell imaging demonstrated that both green fluorescent protein‐fused TFG and mCherry‐fused ALG‐2 are recruited to ERES after thapsigargin treatment, which raises intracellular Ca2+ levels. Furthermore, overexpression of ALG‐2 induced the accumulation of TFG at ERES. TFG has an ALG‐2‐binding motif and deletion of the motif decreased TFG binding to ALG‐2 and shortened its half‐life at ERES, suggesting a critical role for ALG‐2 in retaining TFG at ERES. We also demonstrated, by in vitro cross‐linking assays, that ALG‐2 promoted the polymerization of TFG in a Ca2+‐dependent manner. Collectively, the results suggest that ALG‐2 acts as a Ca2+‐sensitive adaptor to concentrate and polymerize TFG at ERES, supporting a potential role for ALG‐2 in COPII‐dependent trafficking from the endoplasmic reticulum.

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Multifaceted roles of PDCD6 both within and outside the cell

Zhu,

2024

Journal Cellular Physiology

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Programmed cell death protein 6 (PDCD6) is an evolutionarily conserved Ca2+‐binding protein. PDCD6 is involved in regulating multifaceted and pleiotropic cellular processes in different cellular compartments. For instance, nuclear PDCD6 regulates apoptosis and alternative splicing. PDCD6 is required for coat protein complex II‐dependent endoplasmic reticulum‐to‐Golgi apparatus vesicular transport in the cytoplasm. Recent advances suggest that cytoplasmic PDCD6 is involved in the regulation of cytoskeletal dynamics and innate immune responses. Additionally, membranous PDCD6 participates in membrane repair through endosomal sorting complex required for transport complex‐dependent membrane budding. Interestingly, extracellular vesicles are rich in PDCD6. Moreover, abnormal expression of PDCD6 is closely associated with many diseases, especially cancer. PDCD6 is therefore a multifaceted but pivotal protein in vivo. To gain a more comprehensive understanding of PDCD6 functions and to focus and stimulate PDCD6 research, this review summarizes key developments in its role in different subcellular compartments, processes, and pathologies.

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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)

Cited by 44 publications

References 54 publications

Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress

Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress

The calcium‐binding protein ALG‐2 promotes endoplasmic reticulum exit site localization and polymerization of Trk‐fused gene (TFG) protein

Multifaceted roles of PDCD6 both within and outside the cell

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