Src activation triggers capacitation and acrosome reaction but not motility in human spermatozoa

Gabriele Varano1, Adriana Lombardi, Giulia Cantini

  • 1Department of Clinical Physiopathology, Endocrinology Unit, DENOTHE Center for Research, Transfer and High Education, University of Florence, Florence, Italy.

Abstract

Insights

Src kinase plays a key role in human sperm activation. This study identifies its presence and function in regulating sperm capacitation, tyrosine phosphorylation, and the acrosome reaction, crucial for male fertility.

Area of Science:

  • Reproductive Biology
  • Molecular Cell Biology
  • Sperm Physiology

Background:

  • Protein tyrosine phosphorylation is vital for sperm activation.
  • The roles of tyrosine kinases in sperm function remain largely unknown.
  • Src kinase presence and function in human spermatozoa were investigated.

Purpose of the Study:

  • To identify and localize Src kinase in human spermatozoa.
  • To investigate the role of Src kinase in sperm activation processes.
  • To determine Src kinase's involvement in capacitation, tyrosine phosphorylation, and acrosome reaction.

Main Methods:

  • Immunodetection and immunoprecipitation using anti-Src antibodies.
  • Immunofluorescence to determine Src kinase localization and active form (pTyr416).
  • Pharmacological inhibition of Src kinase using SU6656 to assess functional impact.

Main Results:

  • Src kinase (approx. 70 kDa) localized to the post-acrosomal region, neck, and midpiece.
  • Active Src kinase levels increased during sperm capacitation.
  • Src kinase inhibition reduced tyrosine phosphorylation, blocked progesterone-induced acrosome reaction, and interfered with calcium signaling.

Conclusions:

  • A novel Src isoform is identified in human spermatozoa.
  • Src kinase is involved in regulating sperm capacitation and tyrosine phosphorylation.
  • Src kinase plays a critical role in calcium fluxes and the acrosome reaction.

Related Concept Videos

Spermatogenesis01:41

Spermatogenesis

Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of seminiferous tubules. These spermatogonial stem cells divide asymmetrically to give rise to additional stem cells (meaning that these structures “self-renew”), as well as sperm progenitors, called spermatocytes. Importantly, this method of asymmetric mitotic division maintains a population of spermatogonial stem cells in the male reproductive...
Spermatogenesis01:22

Spermatogenesis

Spermatogenesis is a complex process that involves the development of sperm cells from undifferentiated stem cells in the seminiferous tubules of the testes. The process is essential for the production of mature and functional sperm cells that are capable of fertilizing an egg.
The process of spermatogenesis can be divided into mitosis, meiosis, and spermiogenesis. During mitosis, the spermatogonia or stem cells divide to produce two identical daughter cells, type A and B spermatogonia. Type-A...
Fertilization01:38

Fertilization

During fertilization, an egg and sperm cell fuse to create a new diploid structure. In humans, the process occurs once the egg has been released from the ovary, and travels into the fallopian tubes. The process requires several key steps: 1) sperm present in the genital tract must locate the egg; 2) once there, sperm need to release enzymes to help them burrow through the protective zona pellucida of the egg; and 3) the membranes of a single sperm cell and egg must fuse, with the sperm...
Sperm Transport01:15

Sperm Transport

The journey of sperm from its origin to the point of ejaculation begins within the seminiferous tubules of the testis. Here, Sertoli cells produce fluid that propels non-motile sperm through a series of conduits, starting with the straight tubules leading to the rete testis. This interconnected network of tubules acts as the initial pathway for sperm, guiding them into the efferent ductules and then into the epididymis for maturation.
The maturation phase occurs in the epididymis, where sperm...
Yeast Signaling01:28

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...