Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicular transport, cell junction formation, protein anchoring, and spermiation. Here, we show that a junction-mediating and actin-regulatory protein (JMY) affects the blood-tissue barrier (BTB) function through remodeling of the Sertoli cell junctional integrity and it also contributes to controlling endocytic vesicle trafficking. These functions are critical for the maintenance of sperm fertility since loss of Sertoli cell-specific Jmy function induced male subfertility in mice. Specifically, these mice have (a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; (b) high incidence of sperm structural deformity; and (c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell BTB junctional integrity. In addition, JMY interaction with actin-binding protein candidates a-actinin1 and sorbin and SH3 domain containing protein 2 was related to JMY activity, and in turn, actin cytoskeletal organization. In summary, JMY affects the control of spermatogenesis through the regulation of actin filament organization and endocytic vesicle trafficking in Sertoli cells.
Atherosclerosis (AS) is a chronic inflammatory disease seriously endangering human health, whose occurrence and development is related to many factors. Pyroptosis is a recently identified novel programmed cell death associated with an inflammatory response and involved in the formation and progression of AS by activating different signaling pathways. Protein modifications of the sirtuin family and microRNAs (miRNAs) can directly or indirectly affect pyroptosis-related molecules. It is important to link atherosclerosis, thermogenesis and molecular modifications. This article will systematically review the molecular pathways of pyroptosis in AS, which can provide a new perspective for AS prevention and treatment.
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