Evidence map›Paper›PMID 32051546›Full record

ArticleCell death and differentiation2020

Rab5a activates IRS1 to coordinate IGF-AKT-mTOR signaling and myoblast differentiation during muscle regeneration.

Xiao Xia Cong, Xiu Kui Gao, Xi Sheng Rao, Jie Wen, Xiao Ceng Liu, Yin Pu Shi, Min Yi He, Wei Liang Shen, Yue Shen, Hongwei Ouyang and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
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  19. miR-100-5p Regulates Skeletal Muscle Myogenesis through theInternational journal of molecular sciences · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 4 countries.

Xiao Xia Cong *Department of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Xiu Kui Gao *Department of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.ORCID http://orcid.org/0000-0002-6602-0974
Xi Sheng Rao *Department of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Jie WenDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Xiao Ceng LiuDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Yin Pu ShiDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Min Yi HeDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Wei Liang ShenDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Yue ShenDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Hongwei OuyangDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Ping HuThe Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Boon Chuan LowMechanobiology Institute, Department of Biological Sciences, National University of Singapore, Singapore, 117411, Singapore.
Zhuo Xian MengDepartment of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Yue Hai KeDepartment of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Ming Zhu ZhengDepartment of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Lin Rong LuDr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Yong Heng LiangCollege of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China.
Li Ling ZhengDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. zhengliling@zju.edu.cn.
Yi Ting ZhouDepartment of Biochemistry and Molecular Biology and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. zhouyt@zju.edu.cn.ORCID http://orcid.org/0000-0003-4543-3099
Second Affiliated Hospital of Zhejiang University · CNZhejiang University · CNInstitute for Stem Cell Biology and Regenerative Medicine · INChinese Academy of Sciences · CNNanjing Agricultural University · CNNational University of Singapore · SGZhejiang University-University of Edinburgh Institute · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rab5 is a master regulator for endosome biogenesis and transport while its in vivo physiological function remains elusive. Here, we find that Rab5a is upregulated in several in vivo and in vitro myogenesis models. By generating myogenic Rab5a-deficient mice, we uncover the essential roles of Rab5a in regulating skeletal muscle regeneration. We further reveal that Rab5a promotes myoblast differentiation and directly interacts with insulin receptor substrate 1 (IRS1), an essential scaffold protein for propagating IGF signaling. Rab5a interacts with IRS1 in a GTP-dependent manner and this interaction is enhanced upon IGF-1 activation and myogenic differentiation. We subsequently identify that the arginine 207 and 222 of IRS1 and tyrosine 82, 89, and 90 of Rab5a are the critical amino acid residues for mediating the association. Mechanistically, Rab5a modulates IRS1 activation by coordinating the association between IRS1 and the IGF receptor (IGFR) and regulating the intracellular membrane targeting of IRS1. Both myogenesis-induced and IGF-evoked AKT-mTOR signaling are dependent on Rab5a. Myogenic deletion of Rab5a also reduces the activation of AKT-mTOR signaling during skeletal muscle regeneration. Taken together, our study uncovers the physiological function of Rab5a in regulating muscle regeneration and delineates the novel role of Rab5a as a critical switch controlling AKT-mTOR signaling by activating IRS1.

Indexed as

Cell DifferentiationAnimalsCell LineHEK293 CellsHindlimbHumansInsulin-Like Growth Factor IInsulin Receptor Substrate ProteinsIntracellular MembranesMice, Inbred C57BLMuscle DevelopmentMuscle, SkeletalMyoblastsProtein BindingProto-Oncogene Proteins c-aktrab5 GTP-Binding ProteinsInsulin-Like Growth Factor IInsulin Receptor Substrate ProteinsProto-Oncogene Proteins c-aktrab5 GTP-Binding ProteinsReceptor, IGF Type 1RNA, Small InterferingTOR Serine-Threonine Kinases

Identifiers

PMID32051546
PMCPMC7370222
OpenAlexW3006425357

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.