Ca2+-stores in sperm: their identities and functions

Costello, Sarah; Michelangeli, Francesco; Nash, Katherine; Lefièvre, Linda; Morris, Jennifer; Machado-Oliveira, Gisela; Barratt, Christopher L.R.; Kirkman-Brown, Jackson; Publicover, Stephen J.

doi:10.1530/rep-09-0134

Cited by 190 publications

(189 citation statements)

References 99 publications

(170 reference statements)

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“…The acrosome behaves as an internal store of releasable calcium (41)(42)(43)(44); efflux from this reservoir through inositol 1,4,5 triphosphate (IP 3 )-sensitive channels is required for the AR initiated by all inducers (32,33,41,45). We had previously demonstrated that Rab3A acts in the AR before the release of calcium from the intracellular store (32).…”

Section: Resultsmentioning

confidence: 99%

Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis

Bustos

Lucchesi

Ruete

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Two so-called “secretory Rabs,” Rab3 and Rab27, regulate late steps during dense-core vesicle exocytosis in neuroendocrine cells. Sperm contain a single large dense-core granule that is released by regulated exocytosis (termed the acrosome reaction) during fertilization or on exposure to inducers in vitro. Sperm exocytosis uses the same fusion machinery as neurons and neuroendocrine cells, with an additional requirement for active Rab3. Here we show that Rab27 is also required for the acrosome reaction, as demonstrated by the inability of inducers to elicit exocytosis when streptolysin O-permeabilized human sperm were loaded with inhibitory anti-Rab27 antibodies or the Rab27–GTP binding domain of the effector Slac2-b. The levels of GTP-bound Rab27 increased on initiation of exocytosis, as did the proportion of GTP-bound Rab3A. We have developed a fluorescence microscopy-based method for detecting endogenous Rab3A-GTP and Rab27-GTP in the acrosomal region of human sperm. Challenge with an inducer increased the population of cells exhibiting GTP-bound Rabs in this subcellular domain. Interestingly, introducing recombinant Rab27A loaded with GTP-γ-S into sperm elicited a remarkable increase in the number of cells evincing GTP-bound Rab3A. In the converse condition, recombinant Rab3A did not modify the percentage of Rab27-GTP–containing cells. Furthermore, Rab27A-GTP recruited a Rab3 GDP/GTP exchange factor (GEF) activity. Our findings suggest that Rab27/Rab3A constitutes a Rab-GEF cascade in dense-core vesicle exocytosis.

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Section: Resultsmentioning

confidence: 99%

Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis

Bustos

Lucchesi

Ruete

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The physiologically relevant AR changes in [Ca 2+ ] i include external and internal Ca 2+ sources (Breitbart et al 2010 ;Costello et al 2009 ;Darszon et al 2011 ;Florman et al 2008 ). At the present time three different Ca 2+ channels are thought to mediate the [Ca 2+ ] i responses associated to the AR.…”

Section: The Acrosome Reactionmentioning

confidence: 95%

“…Evidence indicates internal Ca 2+ stores (i.e., the acrosome) participate releasing Ca 2+ through the IP3 receptor, the second type of Ca 2+ channel involved in the AR, which is activated as a consequence of IP3 production during the AR Florman et al 2008 ;Mayorga et al 2007 ;Publicover et al 2007 (Costello et al 2009 ;Darszon et al 2012 ).…”

Section: The Acrosome Reactionmentioning

confidence: 99%

Cl− Channels and Transporters in Sperm Physiology

Treviño

Orta

Figueiras-Fierro

et al. 2014

Sexual Reproduction in Animals and Plants

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Spermatozoa must decode environmental and cellular cues to succeed in fertilization, and this process relies heavily on ion channels. New observations bring to light the relevant participation of Cl − channels and anion transporters in some of the main sperm functions. Here we review the evidence that indicates the participation of Cl − channels in motility, maturation, and the acrosome reaction (AR), and what is known about their molecular identity and regulation. Our better understanding of sperm anion transport will yield tools to handle some infertility problems, improve animal breeding and preserve biodiversity, and develop selective and secure male contraceptives.

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“…An example of this is the regulation of calcium by the cell which is clearly critical for key physiological processes, e.g., motility and acrosome reaction. Whilst our knowledge of how calcium is regulated in the cell has increased substantially, 27,28 there are still fundamental gaps, e.g., the role of the putative calcium stores in the sperm neck/midpiece region. However, decades of clinical research suggest that calcium regulation can potentially be used as a tool for identifying dysfunctional cells.…”

Section: Sperm Dysfunction-old Tests Lying Dormant?mentioning

confidence: 99%

Diagnostic tools in male infertility—the question of sperm dysfunction

Barratt¹,

Mansell²,

Beaton³

et al. 2010

Asian J Androl

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Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitro to improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that: (i) there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; (ii) technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap (or more appropriately termed cost effective), easy to use and clinically useful; and (iii) clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one. Keywords: gamete biomarker; male fertility; sperm biomarker; sperm dysfunction INTRODUCTION Infertility is a significant global problem affecting approximately 80 million (1:7) couples worldwide. 1 In a landmark study by Mike Hull and colleagues, in which a representative British population was studied, sperm dysfunction (lacking 'normal' function) was identified as the single most common cause of infertility. 2 Subsequent studies have confirmed these observations 3 and highlighted dysfunctional cells in men with 'normal' semen parameters and conversely normal sperm function in oligozoospermic men. 4 What is remarkable is that, for this group, there is no drug a man can take or add to his spermatozoa in vitro to improve fertility. The only option is assisted reproductive technology (ART) which usually consists of a graduation of treatment depending on severity, i.e., intrauterine insemination for mild, in vitro fertilisation (IVF) for moderate and intracytoplasmic sperm injection (ICSI) for men with severe sperm dysfunction. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. The purpose of this paper is to review the current state of the field and provide insights for further development. The initial focus is on the value of semen analysis as a clinical tool with the discussion progressing to examining sperm dysfunction in detail.

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Ca2+-stores in sperm: their identities and functions

Cited by 190 publications

References 99 publications

Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis

Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis

Cl− Channels and Transporters in Sperm Physiology

Diagnostic tools in male infertility—the question of sperm dysfunction

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