2. Academic Validation
  3. A Novel Dysferlin-Binding Kinase CK2α Promotes Plasma Membrane Repair in Dysferlinopathy

A Novel Dysferlin-Binding Kinase CK2α Promotes Plasma Membrane Repair in Dysferlinopathy

  • FASEB J. 2026 Mar 31;40(6):e71677. doi: 10.1096/fj.202500773RRR.
Naoko Nakamura 1,  Naoki Suzuki 1 2,  Shin-Ichiro Kanno 3,  Rei Yamanaka 4,  Hiroya Ono 1 5 6,  Rumiko Izumi 1,  Rui Muliang 2,  Christian Borgo 7 8,  Akiyuki Ohno 1,  Ryuhei Harada 1,  Saki Saito 1,  Yukino Funayama 1,  Kensuke Ikeda 1,  Shio Mitsuzawa 1,  Yasuaki Watanabe 1,  Tomomi Shijo 1,  Tetsuya Akiyama 1,  Toshiaki Takahashi 9,  Makoto Kanzaki 10,  Shion Osana 11,  Hitoshi Warita 1,  Yoshitsugu Aoki 6,  Satoru Ebihara 2,  Mauro Salvi 7,  Ryoichi Nagatomi 12,  Akira Yasui 3,  Katsuya Miyake 4,  Masashi Aoki 1
Affiliations

Affiliations

  • 1 Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
  • 2 Department of Rehabilitation Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
  • 3 The Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
  • 4 Institute of Basic Medical Research, International University of Health and Welfare, Narita, Chiba, Japan.
  • 5 National Hospital Organization Iwate National Hospital, Ichinoseki, Iwate, Japan.
  • 6 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
  • 7 Department of Biomedical Sciences, University of Padua, Padua, Italy.
  • 8 Department of Medicine, University of Padua, Padua, Italy.
  • 9 National Hospital Organization Sendai Nishitaga Hospital, Sendai, Miyagi, Japan.
  • 10 Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi, Japan.
  • 11 Graduate School of Emergency Medical System, Kokushikan University, Tama, Tokyo, Japan.
  • 12 Designing Future Health Initiative (DFHI), Promotion Office of Strategic Innovation, Tohoku University, Sendai, Miyagi, Japan.
PMID: 41824290 DOI: 10.1096/fj.202500773RRR
Abstract

Dysferlinopathy is an adult-onset form of muscular dystrophy caused by mutations in the dysferlin gene and is inherited in an autosomal recessive manner. Dysferlin is primarily known for its role in plasma membrane repair. Although several proteins associated with dysferlin have been identified, many aspects of its signaling pathways and protein-protein interactions remain unclear. Here, we focused on the region between the third and fourth C2 domains, where frequent genetic mutations occur and functional domains are concentrated, and identified the protein kinase CK2α (formerly known as Casein Kinase 2) as a novel dysferlin-binding protein. CK2α was found to accumulate at membrane injury sites along with dysferlin in mouse skeletal muscle, and membrane repair was delayed in CK2α knockout cells. Furthermore, overexpression of CK2α in dysferlin-deficient mouse muscle led to improved membrane repair. Additionally, we revealed that CK2α plays a role in phosphorylating annexin A1, which is known to bind to dysferlin and is involved in plasma membrane repair. Our results indicated that CK2α controls membrane repair by participating in the phosphorylation of annexin A1. The molecular interplay among dysferlin, CK2α, and phosphorylated annexin A1 represents a novel therapeutic target for promoting membrane repair.

Keywords

Dysferlinopathy; annexin A1; plasma membrane repair; protein kinase CK2; skeletal muscle.

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