PMID- 38327785
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 27
IP  - 2
DP  - 2024 Feb 16
TI  - Calcium-binding protein 7 expressed in muscle negatively regulates age-related 
      degeneration of neuromuscular junctions in mice.
PG  - 108997
LID - 10.1016/j.isci.2024.108997 [doi]
LID - 108997
AB  - The neuromuscular junction (NMJ) forms centrally in myotubes and, as the only 
      synapse between motor neuron and myotube, are indispensable for motor activity. 
      The midmuscle formation of NMJs, including midmuscle-restricted expression of 
      NMJ-related genes, is governed by the muscle-specific kinase (MuSK). However, 
      mechanisms underlying MuSK-mediated signaling are unclear. Here, we find that the 
      Calcium-binding protein 7 (Cabp7) gene shows midmuscle-restricted expression, and 
      muscle-specific depletion of Cabp7 in mice accelerated age-related NMJ 
      degeneration, muscle weakness/atrophy, and motor dysfunction. Surprisingly, 
      forced expression in muscle of CIP, an inhibitory peptide of the negative 
      regulator of NMJ formation cyclin-dependent kinase 5 (Cdk5), restored NMJ 
      integrity and muscle strength, and healed muscle atrophy in muscle-specific 
      Cabp7-deficient mice, which showed increased muscle expression of the Cdk5 
      activator p25. These findings together demonstrate that MuSK-mediated signaling 
      induces muscle expression of Cabp7, which suppresses age-related NMJ degeneration 
      likely by attenuating p25 expression, providing insights into 
      prophylactic/therapeutic intervention against age-related motor dysfunction.
CI  - (c) 2024 The Author(s).
FAU - Eguchi, Takahiro
AU  - Eguchi T
AD  - Division of Genetics, The Institute of Medical Science, The University of Tokyo, 
      Tokyo 108-8639, Japan.
FAU - Tezuka, Tohru
AU  - Tezuka T
AD  - Division of Genetics, The Institute of Medical Science, The University of Tokyo, 
      Tokyo 108-8639, Japan.
FAU - Watanabe, Yuji
AU  - Watanabe Y
AD  - Medical Proteomics Laboratory, The Institute of Medical Science, The University 
      of Tokyo, Tokyo 108-8639, Japan.
FAU - Inoue-Yamauchi, Akane
AU  - Inoue-Yamauchi A
AD  - Division of Genetics, The Institute of Medical Science, The University of Tokyo, 
      Tokyo 108-8639, Japan.
FAU - Sagara, Hiroshi
AU  - Sagara H
AD  - Medical Proteomics Laboratory, The Institute of Medical Science, The University 
      of Tokyo, Tokyo 108-8639, Japan.
FAU - Ozawa, Manabu
AU  - Ozawa M
AD  - Laboratory of Reproductive Systems Biology, The Institute of Medical Science, The 
      University of Tokyo, Tokyo 108-8639, Japan.
AD  - Core Laboratory for Developing Advanced Animal Models, The Institute of Medical 
      Science, The University of Tokyo, Tokyo 108-8639, Japan.
FAU - Yamanashi, Yuji
AU  - Yamanashi Y
AD  - Division of Genetics, The Institute of Medical Science, The University of Tokyo, 
      Tokyo 108-8639, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240126
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC10847746
OTO - NOTNLM
OT  - Molecular biology
OT  - Neuroscience
OT  - Physiology
COIS- The authors declare no competing interests.
EDAT- 2024/02/08 06:43
MHDA- 2024/02/08 06:44
PMCR- 2024/01/26
CRDT- 2024/02/08 04:10
PHST- 2023/08/30 00:00 [received]
PHST- 2023/12/05 00:00 [revised]
PHST- 2024/01/19 00:00 [accepted]
PHST- 2024/02/08 06:44 [medline]
PHST- 2024/02/08 06:43 [pubmed]
PHST- 2024/02/08 04:10 [entrez]
PHST- 2024/01/26 00:00 [pmc-release]
AID - S2589-0042(24)00218-9 [pii]
AID - 108997 [pii]
AID - 10.1016/j.isci.2024.108997 [doi]
PST - epublish
SO  - iScience. 2024 Jan 26;27(2):108997. doi: 10.1016/j.isci.2024.108997. eCollection 
      2024 Feb 16.