Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility

Mammalian fertilization is a complex process involving a series of successive sperm-egg interaction steps mediated by different molecules and mechanisms. Studies carried out during the past 30 years, using a group of proteins named CRISP (Cysteine-RIch Secretory Proteins), have significantly contrib...

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Autores principales: Gonzalez, Soledad N., Sulzyk, Valeria, Weigel Muñoz, Mariana, Cuasnicu, Patricia S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712725/
https://www.ncbi.nlm.nih.gov/pubmed/34970552
http://dx.doi.org/10.3389/fcell.2021.800351
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author Gonzalez, Soledad N.
Sulzyk, Valeria
Weigel Muñoz, Mariana
Cuasnicu, Patricia S.
author_facet Gonzalez, Soledad N.
Sulzyk, Valeria
Weigel Muñoz, Mariana
Cuasnicu, Patricia S.
author_sort Gonzalez, Soledad N.
collection PubMed
description Mammalian fertilization is a complex process involving a series of successive sperm-egg interaction steps mediated by different molecules and mechanisms. Studies carried out during the past 30 years, using a group of proteins named CRISP (Cysteine-RIch Secretory Proteins), have significantly contributed to elucidating the molecular mechanisms underlying mammalian gamete interaction. The CRISP family is composed of four members (i.e., CRISP1-4) in mammals, mainly expressed in the male tract, present in spermatozoa and exhibiting Ca(2+) channel regulatory abilities. Biochemical, molecular and genetic approaches show that each CRISP protein participates in more than one stage of gamete interaction (i.e., cumulus penetration, sperm-ZP binding, ZP penetration, gamete fusion) by either ligand-receptor interactions or the regulation of several capacitation-associated events (i.e., protein tyrosine phosphorylation, acrosome reaction, hyperactivation, etc.) likely through their ability to regulate different sperm ion channels. Moreover, deletion of different numbers and combination of Crisp genes leading to the generation of single, double, triple and quadruple knockout mice showed that CRISP proteins are essential for male fertility and are involved not only in gamete interaction but also in previous and subsequent steps such as sperm transport within the female tract and early embryo development. Collectively, these observations reveal that CRISP have evolved to perform redundant as well as specialized functions and are organized in functional modules within the family that work through independent pathways and contribute distinctly to fertility success. Redundancy and compensation mechanisms within protein families are particularly important for spermatozoa which are transcriptionally and translationally inactive cells carrying numerous protein families, emphasizing the importance of generating multiple knockout models to unmask the true functional relevance of family proteins. Considering the high sequence and functional homology between rodent and human CRISP proteins, these observations will contribute to a better understanding and diagnosis of human infertility as well as the development of new contraceptive options.
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spelling pubmed-87127252021-12-29 Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility Gonzalez, Soledad N. Sulzyk, Valeria Weigel Muñoz, Mariana Cuasnicu, Patricia S. Front Cell Dev Biol Cell and Developmental Biology Mammalian fertilization is a complex process involving a series of successive sperm-egg interaction steps mediated by different molecules and mechanisms. Studies carried out during the past 30 years, using a group of proteins named CRISP (Cysteine-RIch Secretory Proteins), have significantly contributed to elucidating the molecular mechanisms underlying mammalian gamete interaction. The CRISP family is composed of four members (i.e., CRISP1-4) in mammals, mainly expressed in the male tract, present in spermatozoa and exhibiting Ca(2+) channel regulatory abilities. Biochemical, molecular and genetic approaches show that each CRISP protein participates in more than one stage of gamete interaction (i.e., cumulus penetration, sperm-ZP binding, ZP penetration, gamete fusion) by either ligand-receptor interactions or the regulation of several capacitation-associated events (i.e., protein tyrosine phosphorylation, acrosome reaction, hyperactivation, etc.) likely through their ability to regulate different sperm ion channels. Moreover, deletion of different numbers and combination of Crisp genes leading to the generation of single, double, triple and quadruple knockout mice showed that CRISP proteins are essential for male fertility and are involved not only in gamete interaction but also in previous and subsequent steps such as sperm transport within the female tract and early embryo development. Collectively, these observations reveal that CRISP have evolved to perform redundant as well as specialized functions and are organized in functional modules within the family that work through independent pathways and contribute distinctly to fertility success. Redundancy and compensation mechanisms within protein families are particularly important for spermatozoa which are transcriptionally and translationally inactive cells carrying numerous protein families, emphasizing the importance of generating multiple knockout models to unmask the true functional relevance of family proteins. Considering the high sequence and functional homology between rodent and human CRISP proteins, these observations will contribute to a better understanding and diagnosis of human infertility as well as the development of new contraceptive options. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8712725/ /pubmed/34970552 http://dx.doi.org/10.3389/fcell.2021.800351 Text en Copyright © 2021 Gonzalez, Sulzyk, Weigel Muñoz and Cuasnicu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Gonzalez, Soledad N.
Sulzyk, Valeria
Weigel Muñoz, Mariana
Cuasnicu, Patricia S.
Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility
title Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility
title_full Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility
title_fullStr Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility
title_full_unstemmed Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility
title_short Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility
title_sort cysteine-rich secretory proteins (crisp) are key players in mammalian fertilization and fertility
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712725/
https://www.ncbi.nlm.nih.gov/pubmed/34970552
http://dx.doi.org/10.3389/fcell.2021.800351
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