CAMSAP2 is a microtubule minus-end targeting protein (-TIP) that regulates BTB dynamics through cytoskeletal organization

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Article (peer-reviewed)

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During spermatogenesis, microtubule (MT) cytoskeleton in Sertoli cells confers blood-testis barrier (BTB) function, but the regulator(s) and the mechanism(s) that modulate MT dynamics remains unexplored. Herein, we examined the role of CAMSAP2 (calmodulin-regulated spectrin-associated protein 2, a member of the CAMSAP/Patronin protein family), also a minis (-) end-targeting protein (-TIP) that binds to the minus-end (i.e., slow growing end) of polarized MTs involved in determining MT length, in Sertoli cell function. CAMSAP2 was found to localize at discrete sites across the Sertoli cell cytosol, different from EB1 (end binding protein 1, a microtubule plus (+)-end tracking protein, +TIP, that binds to the plus (+)-end of MTs), and co-localized with MTs. CAMSAP2 displayed stage-specific expression pattern, appearing as track-like structures across the seminiferous epithelium in adult rat testes that laid perpendicular to the basement membrane. CAMSAP2 knockdown by RNAi was found to promote Sertoli cell tight junction (TJ)-barrier function, illustrating its role in TJ remodeling under physiological conditions. To further examine the regulatory role of CAMSAP2 in BTB dynamics, we used a PFOS-induced Sertoli cell injury model for studies. CAMSAP2 knockdown blocked PFOS-induced Sertoli cell injury by promoting proper distribution of BTB-associated proteins at the cell-cell interface. This effect was mediated by the ability of CAMSAP2 knockdown to block PFOS-induced disruptive organization of MTs, but also F-actin, across cell cytosol through changes in cellular distribution/localization of MT and actin regulatory proteins. In summary, CAMSAP2 is a regulator of MT and actin dynamics in Sertoli cells to support BTB dynamics and spermatogenesis.