Connexins in skeletal muscle development and disease

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• 作者：Peter A. Merrifield ; ^{pmerrifi@uwo.ca" class="auth_mail" title="E-mail the corresponding author} ; Dale W. Laird¹ ; ^{dale.laird@schulich.uwo.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ATP ; adenosine triphosphate ; Cx39 ; connexin39 ; Cx40 ; connexin40 ; Cx43 ; connexin43 ; Cx45 ; connexin45 ; GJIC ; gap junctional intercellular communication ; Myf5 ; myogenic factor 5 ; MRF4 ; myogenic regulatory factor 4 ; ODDD ; oculodentodigital dysplasia ; pax7 ; paired box 7 ; TRPC1 ; transient receptor potential canonical 1.
• 刊名：Seminars in Cell & Developmental Biology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：50
• 期：Complete
• 页码：67-73
• 全文大小：1922 K

文摘

Gap junctions consist of clusters of intercellular channels composed of connexins that connect adjacent cells and allow the exchange of small molecules. While the 21 member multi-gene family of connexins are ubiquitously found in humans, only Cx39, Cx40, Cx43 and Cx45 have been documented in developing myoblasts and injured adult skeletal muscle while healthy adult skeletal muscle is devoid of connexins. The use of gap junctional blockers and cultured myoblast cell lines have suggested that these connexins play a critical role in myotube formation and muscle regeneration. More recent genetically-modified mouse models where Cx43 function is greatly compromized or ablated have further supported a role for Cx43 in regulating skeletal muscle development. In the last decade, we have become aware of a cohort of patients that have a development disorder known as oculodentodigital dysplasia (ODDD). These patients harbor either gain or loss of Cx43 function gene mutations that result in many organ anomalies raising questions as to whether they suffer from defects in skeletal muscle formation or regeneration upon injury. Interesting, some ODDD patients report muscle weakness and loss of limb control but it is not clear if this is neurogenic or myogenic in origin. This review will focus on the role connexins play in muscle development and repair and discuss the impact of Cx43 mutants on muscle function.