The Fer tyrosine kinase protects sperm from spontaneous acrosome reaction. 2022

Elina Grinshtain, and Sally Shpungin, and Micha Baum, and Uri Nir, and Haim Breitbart
The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.

The physiological acrosome reaction occurs after mammalian spermatozoa undergo a process called capacitation in the female reproductive tract. Only acrosome reacted spermatozoon can penetrate the egg zona-pellucida and fertilize the egg. Sperm also contain several mechanisms that protect it from undergoing spontaneous acrosome reaction (sAR), a process that can occur in sperm before reaching proximity to the egg and that abrogates fertilization. We previously showed that calmodulin-kinase II (CaMKII) and phospholipase D (PLD) are involved in preventing sAR through two distinct pathways that enhance F-actin formation during capacitation. Here, we describe a novel additional pathway involving the tyrosine kinase Fer in a mechanism that also prevents sAR by enhancing actin polymerization during sperm capacitation. We further show that protein-kinase A (PKA) and the tyrosine-kinase Src, as well as PLD, direct Fer phosphorylation/activation. Activated Fer inhibits the Ser/Thr phosphatase PP1, thereby leading to CaMKII activation, actin polymerization, and sAR inhibition.

UI MeSH Term Description Entries
D008297 Male Males
D008322 Mammals Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young. Mammalia,Mammal
D010739 Phospholipase D An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4. Lecithinase D,Phosphatidylcholine Phosphohydrolase
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D005260 Female Females
D000177 Acrosome The cap-like structure covering the anterior portion of SPERM HEAD. Acrosome, derived from LYSOSOMES, is a membrane-bound organelle that contains the required hydrolytic and proteolytic enzymes necessary for sperm penetration of the egg in FERTILIZATION. Acrosomes
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013075 Sperm Capacitation The structural and functional changes by which SPERMATOZOA become capable of oocyte FERTILIZATION. It normally requires exposing the sperm to the female genital tract for a period of time to bring about increased SPERM MOTILITY and the ACROSOME REACTION before fertilization in the FALLOPIAN TUBES can take place. Capacitation of Spermatozoa,Capacitation, Sperm,Spermatozoa Capacitation
D013094 Spermatozoa Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility. Sperm,Spermatozoon,X-Bearing Sperm,X-Chromosome-Bearing Sperm,Y-Bearing Sperm,Y-Chromosome-Bearing Sperm,Sperm, X-Bearing,Sperm, X-Chromosome-Bearing,Sperm, Y-Bearing,Sperm, Y-Chromosome-Bearing,Sperms, X-Bearing,Sperms, X-Chromosome-Bearing,Sperms, Y-Bearing,Sperms, Y-Chromosome-Bearing,X Bearing Sperm,X Chromosome Bearing Sperm,X-Bearing Sperms,X-Chromosome-Bearing Sperms,Y Bearing Sperm,Y Chromosome Bearing Sperm,Y-Bearing Sperms,Y-Chromosome-Bearing Sperms

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