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Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas

Miki Kobayakawa1,2,3, Takuma Matsubara1, Akiko Mizokami4

  • 1Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Japan.

Cell Biochemistry and Function
|December 31, 2019
PubMed

Insights

Osteoclast function, crucial for bone resorption, depends on c-Src and p130Cas. We identified kinesin family protein 1c (Kif1c) as a downstream molecule regulating cytoskeletal organization and bone resorption.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Podosome formation in osteoclasts is essential for bone resorption.
  • Mice lacking c-Src or p130Cas exhibit osteopetrosis due to impaired podosome formation.
  • The c-Src/p130Cas pathway is critical for osteoclast bone resorption.

Purpose of the Study:

  • To identify downstream molecules of the c-Src/p130Cas pathway involved in osteoclast bone resorption.
  • To investigate the role of kinesin family protein 1c (Kif1c) in osteoclast function.

Main Methods:

  • cDNA microarray analysis of osteoclasts from c-Src-/- , p130CasΔOCL-/- , and wild-type mice.
  • siRNA-mediated knockdown and overexpression of Kif1c in osteoclasts.
  • Assessment of podosome formation, actin ring formation, and bone resorption activity.

Main Results:

  • Kif1c expression was downregulated in osteoclasts lacking c-Src or p130Cas.
  • Kif1c knockdown in wild-type osteoclasts suppressed actin ring formation.
  • Kif1c overexpression rescued bone resorption in p130CasΔOCL-/- osteoclasts but not in c-Src-/- osteoclasts.

Conclusions:

  • Kinesin family protein 1c (Kif1c) is a downstream target of the c-Src/p130Cas pathway.
  • Kif1c plays a crucial role in regulating cytoskeletal organization and bone resorption by osteoclasts.
  • Kif1c acts downstream of p130Cas in the regulation of osteoclastic bone resorption.
Keywords:
Kif1cc-Srcosteoclastsp130Caspodosome

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