Besides its capacity to inhibit the 1,4,5-trisphosphate (IP3) receptor, the regulatory protein IRBIT (IP3 receptor binding protein released with IP3) is also able to control the activity of numerous ion channels and electrolyte transporters and thereby creates an optimal electrolyte composition of various biological fluids. Since a reliable execution of spermatogenesis and sperm maturation critically depends on the establishment of an adequate microenvironment, the expression of IRBIT in male reproductive tissue was examined using immunohistochemical approaches combined with biochemical fractionation methods. The present study documents that IRBIT is expressed in Leydig and Sertoli cells. In addition, pronounced IRBIT expression was detected in sperm precursors during early stages of spermatogenesis as well as in spermatozoa. Analyzing tissue sections of rodent epididymides, IRBIT was found to co-localize with the proton pumping V-ATPase and the cystic fibrosis transmembrane conductance regulator (CFTR) at the apical surface of narrow and clear cells. A similar co-localization of IRBIT with CFTR was also observed for Sertoli cells and developing germ cells. Remarkably, assaying caudal sperm in immunogold electron microscopy, IRBIT was found to localize to the acrosomal cap and the flagellum as well as to the sperm nucleus; moreover, a prominent oligomerization was observed for spermatozoa. The pronounced occurrence of IRBIT in the male reproductive system and mature spermatozoa indicates a potential role for IRBIT in establishing the essential luminal environment for a faithful execution of spermatogenesis and epididymal sperm maturation, and suggest a participation of IRBIT during maturation steps after ejaculation and/or the final fertilization process.
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http://dx.doi.org/10.1002/jcp.25209 | DOI Listing |
Biochim Biophys Acta Mol Cell Res
October 2024
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina. Electronic address:
This integrative review aims to highlight the importance of investigating the functional role of AHCYL1, also known as IRBIT, in cancer cells. It has recently been suggested that AHCYL1 regulates cell survival/death, stemness capacity, and the host adaptive response to the tumor microenvironment. Despite this knowledge, the role of AHCYL1 in cancer is still controversial, probably due to its ability to interact with multiple factors in a tissue-specific manner.
View Article and Find Full Text PDFSci Adv
April 2024
Division of Evolutionary Biology, LMU Munich, Planegg-Martinsried, Germany.
PLoS One
May 2023
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, United States of America.
The ER Ca2+ channel ryanodine receptor 2 (RyR2) is required for maintenance of insulin content and glucose-stimulated insulin secretion, in part, via regulation of the protein IRBIT in the insulinoma cell line INS-1. Here, we examined store-operated and depolarization-dependent Ca2+entry using INS-1 cells in which either RyR2 or IRBIT were deleted. Store-operated Ca2+ entry (SOCE) stimulated with thapsigargin was reduced in RyR2KO cells compared to controls, but was unchanged in IRBITKO cells.
View Article and Find Full Text PDFFront Physiol
April 2023
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
The kidney plays a central role in maintaining the fluid and electrolyte homeostasis in the body. Bicarbonate transporters NBCn1, NBCn2, and AE2 are expressed at the basolateral membrane of the medullary thick ascending limb (mTAL). In a previous study, NBCn1, NBCn2, and AE2 are proposed to play as a regulatory pathway to decrease NaCl reabsorption in the mTAL under high salt condition.
View Article and Find Full Text PDFBiol Direct
March 2023
Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET, Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
Background: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown.
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