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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Cell Biochemistry an...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Cell Biochemistry and Function
Article . 2019 . Peer-reviewed
License: Wiley Online Library User Agreement
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Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas

Authors: Miki Kobayakawa; Takuma Matsubara; Akiko Mizokami; Fumitaka Hiura; Nana Takakura; Shoichiro Kokabu; Miho Matsuda; +6 Authors

Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas

Abstract

Podosome formation in osteoclasts is an important initial step in osteoclastic bone resorption. Mice lacking c‐Src (c‐Src−/−) exhibited osteopetrosis due to a lack of podosome formation in osteoclasts. We previously identified p130Cas (Crk‐associated substrate [Cas]) as one of c‐Src downstream molecule and osteoclast‐specific p130Cas‐deficient (p130CasΔOCL−/−) mice also exhibited a similar phenotype to c‐Src−/− mice, indicating that the c‐Src/p130Cas plays an important role for bone resorption by osteoclasts. In this study, we performed a cDNA microarray and compared the gene profiles of osteoclasts from c‐Src−/− or p130CasΔOCL−/− mice with wild‐type (WT) osteoclasts to identify downstream molecules of c‐Src/p130Cas involved in bone resorption. Among several genes that were commonly downregulated in both c‐Src−/− and p130CasΔOCL−/− osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c‐Src−/− and p130CasΔOCL−/− osteoclasts compared with WT osteoclasts. Kif1c exhibited a broad tissue distribution, including osteoclasts. Knockdown of Kif1c expression using shRNAs in WT osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in p130CasΔOCL−/− osteoclasts but not c‐Src−/− osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas (191 words).Significance of the studyWe previously showed that the c‐Src/p130Cas (Cas) plays an important role for bone resorption by osteoclasts. In this study, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization, as a downstream molecule of c‐Src/p130Cas axis, using cDNA microarray. Knockdown of Kif1c expression using shRNAs in wild‐type osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in osteoclast‐specific p130Cas‐deficient (p130CasΔOCL−/−) osteoclasts but not c‐Src−/− osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas.

Keywords

Heterozygote, Macrophage Colony-Stimulating Factor, Kinesins, Osteoclasts, Mice, Transgenic, Actins, Bone and Bones, Recombinant Proteins, CSK Tyrosine-Protein Kinase, Mice, Crk-Associated Substrate Protein, HEK293 Cells, Phenotype, Gene Expression Regulation, Animals, Humans, Bone Resorption, Phosphorylation, RNA, Small Interfering, Oligonucleotide Array Sequence Analysis

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Top 10%
Average
Top 10%
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