A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella.

Wei Li,Darrell L Peterson,Zhibing Zhang,David C Williams,Waixing Tang,Maria E Teves,Ling Zhang,Hongfei Li,Jerome F Strauss,Zhengang Zhang,Kellie J Archer

doi:10.1242/dev.119834

Abstract

A key event in the process of spermiogenesis is the formation of the flagella, which enables sperm to reach eggs for fertilization. Yeast two-hybrid studies revealed that meiosis-expressed gene 1 (MEIG1) and Parkin co-regulated gene (PACRG) interact, and that sperm-associated antigen 16, which encodes an axoneme central apparatus protein, is also a binding partner of MEIG1. In spermatocytes of wild-type mice, MEIG1 is expressed in the whole germ cell bodies, but the protein migrates to the manchette, a unique structure at the base of elongating spermatid that directs formation of the flagella. In the elongating spermatids of wild-type mice, PACRG colocalizes with α-tubulin, a marker for the manchette, whereas this localization was not changed in the few remaining elongating spermatids of Meig1-deficient mice. In addition, MEIG1 no longer localizes to the manchette in the remaining elongating spermatids of Pacrg-deficient mice, indicating that PACRG recruits MEIG1 to the manchette. PACRG is not stable in mammalian cells, but can be stabilized by MEIG1 or by inhibition of proteasome function. SPAG16L is present in the spermatocyte cytoplasm of wild-type mice, and in the manchette of elongating spermatids, but in the Meig1 or Pacrg-deficient mice, SPAG16L no longer localizes to the manchette. By contrast, MEIG1 and PACRG are still present in the manchette of Spag16L-deficient mice, indicating that SPAG16L is a downstream partner of these two proteins. Together, our studies demonstrate that MEIG1/PACRG forms a complex in the manchette and that this complex is necessary to transport cargos, such as SPAG16L, to build the sperm flagella.

Highlights

Mouse meiosis-expressed gene 1 (Meig1) was originally identified in a search for mammalian genes involved in meiotic processes (Don and Wolgemuth, 1992)
Even though Meig1 is present in somatic cells in the testis (Ever et al, 1999; Bouma et al, 2007), we discovered that meiosis-expressed gene 1 (MEIG1) regulates spermatogenesis through its role in germ cells, but not in Sertoli cells (Teves et al, 2013)
Our studies demonstrate that MEIG1/Parkin co-regulated gene (PACRG) form a complex in the manchette, and this complex is essential to transport sperm flagella proteins, such as SPAG16L, to build sperm flagella

Summary

Introduction

Mouse meiosis-expressed gene 1 (Meig1) was originally identified in a search for mammalian genes involved in meiotic processes (Don and Wolgemuth, 1992). MEIG1 in meiosis, and two Meig cDNAs encoding the same protein were identified. The MEIG1 protein appears to form dimers of 31 kDa and 32 kDa, and the 31 kDa dimeric form enters the nucleus during the first meiotic prophase and binds to the meiotic chromatin (Steiner et al, 1999). It has been reported that Meig mRNA is expressed in germ cells, and in somatic cells (Ever et al, 1999; Steiner et al, 1999)

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Conclusion