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Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: killing three birds with one stone.

Authors
Sutovsky-P
Source
Microsc Res Tech 2003 May; 61(1):88-102
NIOSHTIC No.
20038189
Abstract
Ubiquitin and ubiquitin-like proteins control the degradation of substrates as diverse as cyclins, viral envelope proteins, plasma membrane receptors, and mRNAs. The ubiquitinated substrates are targeted towards the lysosomal or proteasomal degradation sites. The number and position of ubiquitin molecules bound to substrates' lysine residues and the number and position of ubiquitin molecules in polyubiquitin chains determine the astonishing substrate specificity of ubiquitin-mediated proteolysis. Ubiquitin is likely to be expressed in mammalian gametes and embryos at any given developmental step, but the information on ubiquitin dependence of gametogenesis and fertilization is sketchy. Ubiquitin ligases E1, E2, E3, and UBC4 are active in the testis. Ubiquitin and proteasomal subunits can be detected in the human sperm centrosome that undergoes dramatic reduction during spermatid elongation. Spermatid histones are ubiquitinated as they are being transiently replaced by transitional proteins and permanently by protamines. Ubiquitin tagging of the sperm mitochondrial membranes may serve as a death sentence for paternal mitochondria at fertilization, thus promoting the maternal inheritance of mitochondrial DNA (mtDNA) in mammals. The defective spermatozoa become surface-ubiquitinated during sperm descent down the epididymis. Finally, new evidence suggests the involvement of ubiquitin-proteasome pathway in the zona penetration by the acrosome-reacted spermatozoon. Such differential patterns of ubiquitination in the testis and epididymis, and inside the egg, may be necessary for reproductive success in humans and animals. Deciphering and eventually manipulating the ubiquitin-dependent proteolysis in the reproductive system could allow us to redirect the mode of mtDNA inheritance after cloning and ooplasmic transplantation, provide germ line therapy in some cases of male infertility, develop new contraceptives, manage polyspermia during in vitro fertilization, and establish objective markers for infertility diagnostics, semen evaluation, and prediction of future fertility.
Keywords
Reproductive-system-disorders; Reproductive-system; Spermatogenesis; Spermatozoa; Fertility; DNA-damage; Proteins; Author Keywords: ubiquitin; sperm; fertilization; mitochondria; proteasome; epididymis; testis
Contact
Peter Sutovsky, Ph.D., Assistant Professor, University of Missouri-Columbia, S141 ASRC, 920 East Campus Drive Columbia, MO 65211-5300
CODEN
MRTEEO
Publication Date
20030501
Document Type
Journal Article
Email Address
sutovskyp@missouri.edu
Funding Amount
235845
Funding Type
Grant
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R21-OH-007324
Issue of Publication
1
ISSN
1059-910X
Source Name
Microscopy Research and Technique
State
MO
Performing Organization
University of Missouri, Columbia, Missouri
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