Testis

A Novel Testicular RhoGAP-Domain Protein Induces Apoptosis

Abstract
GTPase activating proteins accelerate the hydrolysis of GTP to GDP by small GTPases. GTPases plays diverse roles in many cellular processes including proliferation, cell motility, endocytosis, nuclear import/export and nuclear membrane formation. Little is known about GTPase activating protein (GAP) domain proteins in spermatogenesis. We isolated a novel RhoGAP domain containing protein tGAP1 from male germ cells that exhibits unusual properties. tGAP1 is expressed at low levels in early spermatogonia. Robust transcription initiates in mid-pachytene spermatocytes and continues after meiosis. The 175 kD tGAP1 protein localizes to the cytoplasm of spermatocytes and to cytoplasm and nucleus in spermatids. The protein contains four GAP-domain related sequences in contrast to all other GAP proteins that harbor one such domain. No activity towards RhoA, Rac1 or Cdc42 could be detected. Transfection studies in various somatic cells indicated that low level tGAP1 expression significantly slows down the cell cycle. Expression of higher levels of tGAP1 by infection of somatic cells with recombinant adenoviruses demonstrates that tGAP1 efficiently induces apoptosis, a first such demonstration for a RhoGAP protein. Based on its subcellular location in spermatids and its activity tGAP1 may play a role in nuclear import/export.

Key words: Testis • Apoptosis • Spermatid • Spermatogenesis

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