Focal adhesion kinase is a regulator of F-actin dynamics: New insights from studies in the testis
During spermatogenesis, spermatogonia (2n, diploid) undergo a series of mitotic divisions as well as differentiation to become spermatocytes, which enter meiosis I to be followed by meiosis II to form round spermatids (1n, haploid), and then differentiate into spermatozoa (1n, haploid) via spermiogenesis. These events take place in the epithelium of the seminiferous tubule, involving extensive junction restructuring at the Sertoli–Sertoli and Sertoli-germ cell interface to allow the transport of developing germ cells across the epithelium. Although structural aspects of these cell–cell junctions have been studied, the underlying mechanism(s) that governs these events has yet to be explored. Earlier studies have shown that a non-receptor protein tyrosine kinase known as focal adhesion kinase (FAK) is a likely regulator of these events due to the stage-specific and spatiotemporal expression of its various phosphorylated/activated forms at the testis-specific anchoring junctions in the testis, as well as its association with actin regulatory proteins. Recent studies have shown that FAK, in particular its two activated phosphorylated forms p-FAK-Tyr^407 and p-FAK-Tyr^397, are crucial regulators in modulating junction restructuring at the Sertoli cell–cell interface at the blood–testis barrier (BTB) known as the basal ectoplasmic specialization (basal ES), as well as at the Sertoli–spermatid interface called apical ES during spermiogenesis via its effects on the filamentous (F)-actin organization at the ES. We herein summarize and critically evaluate the current knowledge regarding the physiological significance of FAK in regulating BTB and apical ES dynamics by governing the conversion of actin filaments at the ES from a “bundled” to a "de-bundled/branched" configuration and vice versa. We also provide a molecular model on the role of FAK in regulating these events based on the latest findings in the field.
Li, Stephen Y.T., Dolores D. Mruk, and C. Yan Cheng. 2013. "Focal adhesion kinase is a regulator of F-actin dynamics: New insights from studies in the testis," Spermatogenesis 3(3): e25385.