Actin associated proteins function as androgen receptor coregulators: an implication of androgen receptor's roles in skeletal muscle.
This review of androgen receptor (AR) coregulators, which also function as actin-binding proteins, intends to establish the connection between actin cytoskeletal components and androgen signaling, especially in skeletal muscle. In cellular and animal models, androgen activated AR modulates myoblasts proliferation, promotes sexual dimorphic muscle development, and alters muscle fiber type. In the clinical setting, administration of anabolic androgens can decrease cachexia and speed wound healing. During myogenesis and regeneration of skeletal muscle in embryo and adult, the membrane of myoblasts fuse and the actin cytoskeleton is rearranged to form an alignment with myosin to form myotubes then ultimately the myofibrils. Contraction of skeletal muscle promotes the growth of myocytes by coordinating signals from the neuromuscular junction to intra-myofibrils through costameres, the functional structure comprised of signal proteins closely associated with actin filaments and involved in muscular dystrophy. Therefore, the discovery of actin-binding proteins functioning as AR coregulators implies that androgen signaling is tightly regulated during the process of the development and regeneration of skeletal muscle. The search for selective androgen receptor modulators (SARM) that act precisely in skeletal muscle instead of other tissues could target the engineering of a SARM-AR complex that selectively recruits these coregulators.
Ting
Huei-Ju
HJ
Department of Pathology and Urology, The Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
Chang
Chawnshang
C
D000199:Actins / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D000728:Androgens; D008840:Microfilament Proteins; D011944:Receptors, Androgen