Abstract
According to recent estimates, 2%–15% of couples are sterile, and approximately half of the infertility cases are attributed to male reproductive factors. However, the reasons remain undefined in approximately 25% of male infertility cases, and most infertility cases exhibit spermatogenic defects. Numerous genes involved in spermatogenesis still remain unknown. We previously identified Male Germ Cells Rab GTPase-Activating Proteins (MGCRABGAPs) through cDNA microarray analysis of human testicular tissues with spermatogenic defects. MGCRABGAP contains a conserved RABGAP catalytic domain, TBC (Tre2/Bub2/Cdc16). RABGAP family proteins regulate cellular function (e.g., cytoskeletal remodeling, vesicular trafficking, and cell migration) by inactivating RAB proteins. MGCRABGAP is a male germ cell-specific protein expressed in elongating and elongated spermatids during mammalian spermiogenesis. The purpose of this study was to identify proteins that interact with MGCRABGAP during mammalian spermiogenesis using a proteomic approach. We found that MGCRABGAP exhibited GTPase-activating bioability, and several MGCRABGAP interactors, possible substrates (e.g., RAB10, RAB5C, and RAP1), were identified using co-immunoprecipitation (co-IP) and nano liquid chromatography-mass spectrometry/mass spectrometry (nano LC-MS/MS). We confirmed the binding ability between RAB10 and MGCRABGAP via co-IP. Additionally, MGCRABGAP–RAB10 complexes were specifically colocalized in the manchette structure, a critical structure for the formation of spermatid heads, and were slightly expressed at the midpiece of mature spermatozoa. Based on these results, we propose that MGCRABGAP is involved in mammalian spermiogenesis by modulating RAB10.
Highlights
We identified the human Male Germ Cells Rab GTPase-Activating Proteins (MGCRABGAPs), characterized by the presence of a conserved RABGAP catalytic domain, TBC (Tre2/Bub2/Cdc16) [16]
To delineate whether MGCRABGAP colocalizes with RAB10 during mammalian spermatogenesis, an immunofluorescence assay (IFA) was performed on murine testicular sections
These results indicated that MGCRABGAP interacts with and is colocalized with RAB10 in male germ cells
Summary
It is reported that approximately 2%–15% of couples worldwide are affected by infertility, of which nearly half are attributed to male reproductive factors [1,2]. Male infertility is a multifactorial syndrome encompassing a wide variety of disorders such as anatomic defects, gametogenesis dysfunction, endocrinopathies, immunological problems, ejaculatory failure, environmental exposures, and genetic mutations [3]. The cause is unknown in up to 25% of male infertility cases [4]. Genetic abnormalities leading to male infertility are responsible for 15%–30% of the cases, and it is likely that most cases of idiopathic infertility are constituted by underlying genetic causes [5]. Molecular defects and genetic alterations responsible for male infertility disrupt physiological processes, including hormonal homeostasis, spermatogenesis, and sperm quality [6]. A high number of genes involved in spermatogenesis still remain unknown [7]
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