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Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor

التفاصيل البيبلوغرافية
العنوان: Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor
المؤلفون: Hideyuki Kobayashi, M. Alaa Terkawi, Masahiro Ota, Tomoka Hasegawa, Tomomaya Yamamoto, Tomohiro Shimizu, Dai Sato, Ryo Fujita, Toshifumi Murakami, Norio Amizuka, Norimasa Iwasaki, Masahiko Takahata
المصدر: Bone Research, Vol 12, Iss 1, Pp 1-11 (2024)
بيانات النشر: Nature Publishing Group, 2024.
سنة النشر: 2024
المجموعة: LCC:Biology (General)
LCC:Physiology
مصطلحات موضوعية: Biology (General), QH301-705.5, Physiology, QP1-981
الوصف: Abstract DNAX-associated protein 12 kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis. Although several DAP12-associated receptors (DARs) have been identified in osteoclasts, including triggering receptor expressed on myeloid cells 2 (TREM-2), C-type lectin member 5 A (CLEC5A), and sialic acid-binding Ig-like lectin (Siglec)-15, their precise role in the development of osteoclasts and bone remodeling remain poorly understood. In this study, mice deficient in Trem-2, Clec5a, Siglec-15 were generated. In addition, mice double deficient in these DAR genes and FcεRI gamma chain (FcR)γ, an alternative ITAM adaptor to DAP12, were generated. Bone mass analysis was conducted on all mice. Notably, Siglec-15 deficient mice and Siglec-15/FcRγ double deficient mice exhibited mild and severe osteopetrosis respectively. In contrast, other DAR deficient mice showed normal bone phenotype. Likewise, osteoclasts from Siglec-15 deficient mice failed to form an actin ring, suggesting that Siglec-15 promotes bone resorption principally by modulating the cytoskeletal organization of osteoclasts. Furthermore, biochemical analysis revealed that Sigelc-15 activates macrophage colony-stimulating factor (M-CSF)-induced Ras-associated protein-1 (RAP1)/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway through formation of a complex with p130CAS and CrkII, leading to cytoskeletal remodeling of osteoclasts. Our data provide genetic and biochemical evidence that Siglec-15 facilitates M-CSF-induced cytoskeletal remodeling of the osteoclasts.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2095-6231
Relation: https://doaj.org/toc/2095-6231
DOI: 10.1038/s41413-024-00340-w
URL الوصول: https://doaj.org/article/1f0ebe6fae2b4d6193f234e0f1cc9884
رقم الأكسشن: edsdoj.1f0ebe6fae2b4d6193f234e0f1cc9884
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20956231
DOI:10.1038/s41413-024-00340-w