Plectin stabilizes microtubules during osteoclastic bone resorption by acting as a scaffold for Src and Pyk2
| Autor: | Tatsuki Yaginuma, Yuko Fujita, Izumi Yoshioka, Shoichiro Kokabu, Kenshi Maki, Roland Baron, Hisako Hikiji, Takuma Matsubara, Kouji Watanabe, William N. Addison |
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| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Histology Physiology Endocrinology Diabetes and Metabolism Osteoclasts 030209 endocrinology & metabolism macromolecular substances Microtubules Bone resorption 03 medical and health sciences 0302 clinical medicine Microtubule Osteoclast medicine Humans Bone Resorption Actin Cells Cultured Tartrate-resistant acid phosphatase Rous sarcoma virus biology Chemistry Plectin biology.organism_classification Cell biology 030104 developmental biology medicine.anatomical_structure Focal Adhesion Kinase 2 Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Bone. 132 |
| ISSN: | 1873-2763 |
| Popis: | Osteoclasts are multinuclear cells which maintain bone homeostasis by resorbing bone. During bone resorption, osteoclasts attach to the bone matrix via a sealing zone formed by an actin ring. Rous sarcoma oncogene (Src) is essential for actin ring formation and bone resorption. Recently, we demonstrated that plectin, a cytolinker protein, is a Src-binding protein in osteoclasts. However, the function of plectin in osteoclasts remains unknown. In this study, we demonstrated that shRNA knockdown of plectin in RAW 264.7 cells resulted in tartrate resistant acid phosphatase positive multinuclear cells (TRAP (+) MNCs) with impaired actin ring formation and bone resorption activity. Moreover, we found that in plectin-silenced TRAP (+) MNCs, Src and protein tyrosine kinase 2 beta (Pyk2), two critical kinases in osteoclastic bone resorption, were inactivated and microtubule polarity was disturbed. These results suggest that plectin plays a critical role in osteoclast biology by acting as a scaffold to facilitate Src and Pyk2 activation during microtubule organization. |
| Databáze: | OpenAIRE |
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