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The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition.

Nixon B, Bromfield EG, Dun MD, Redgrove KA, McLaughlin EA, Aitken RJ - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection (ICSI), recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition.While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 (HSPA2), as a key regulator of these events in human spermatozoa.HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization (IVF) success.

View Article: PubMed Central - PubMed

Affiliation: Priority Research Centre in Reproductive Science; Priority Research Centre in Chemical Biology, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.

ABSTRACT
One of the most common lesions present in the spermatozoa of human infertility patients is an idiopathic failure of sperm-egg recognition. Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection (ICSI), recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition. Previous work in this field has established that the sperm domains responsible for oocyte interaction are formed during spermatogenesis prior to being dynamically modified during epididymal maturation and capacitation in female reproductive tract. While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 (HSPA2), as a key regulator of these events in human spermatozoa. HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization (IVF) success. Furthermore, reduced expression of HSPA2 from the human sperm proteome leads to an impaired capacity for cumulus matrix dispersal, sperm-egg recognition and fertilization following both IVF and ICSI. In this review, we consider the evidence supporting the role of HSPA2 in sperm function and explore the potential mechanisms by which it is depleted in the spermatozoa of infertile patients. Such information offers novel insights into the molecular mechanisms governing sperm function.

No MeSH data available.


Related in: MedlinePlus

Functional roles of heat shock proteins (HSP). The evolutionarily conserved molecular chaperones of the HSP70 (HSPA) family fulfill an essential role in maintaining protein quality control in a variety of cell types. Such protective activities center on the ability of the chaperones to assist the correct (re)folding of nascent and denatured proteins, thereby preventing their unwanted aggregation and functional inactivation. However, HSP70s also play an important role in facilitating protein-protein interactions, the assembly of multimeric protein complexes, and in the transport of proteins across intracellular membranes.
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Figure 1: Functional roles of heat shock proteins (HSP). The evolutionarily conserved molecular chaperones of the HSP70 (HSPA) family fulfill an essential role in maintaining protein quality control in a variety of cell types. Such protective activities center on the ability of the chaperones to assist the correct (re)folding of nascent and denatured proteins, thereby preventing their unwanted aggregation and functional inactivation. However, HSP70s also play an important role in facilitating protein-protein interactions, the assembly of multimeric protein complexes, and in the transport of proteins across intracellular membranes.

Mentions: The 70 kDa HSPs (HSP70) are among the most highly abundant and conserved members of the chaperone family, with at least 13 members represented in the human genome.30 These folding catalysts possess a modular architecture comprising three major functional domains: a conserved N-terminal ATPase domain, a substrate-binding domain and a C-terminal domain that acts as a lid for the substrate binding domain.3435 The substrate binding and release cycle of HSP70s is commonly regulated by co-chaperones from the family of J-domain proteins (primarily HSP40 in eukaryotes) that target these chaperones to their respective substrates, and is further fine-tuned by nucleotide exchange factors.36 The primary function of HSP70s centers on their ability to transiently bind to partially synthesized or denatured peptide sequences, thereby preventing their aggregation and allowing them to (re)fold into a functional state. However, by virtue of their ability to stabilize client proteins in a partially folded state, HSP70s also aid in the transmembrane transport of proteins, and in their assembly into functional complexes35 (Figure 1). A novel, testis-enriched member of this HSP70 family, known as HSPA2, has emerged as a key regulator of several phases of sperm development and maturation.263738


The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition.

Nixon B, Bromfield EG, Dun MD, Redgrove KA, McLaughlin EA, Aitken RJ - Asian J. Androl. (2015 Jul-Aug)

Functional roles of heat shock proteins (HSP). The evolutionarily conserved molecular chaperones of the HSP70 (HSPA) family fulfill an essential role in maintaining protein quality control in a variety of cell types. Such protective activities center on the ability of the chaperones to assist the correct (re)folding of nascent and denatured proteins, thereby preventing their unwanted aggregation and functional inactivation. However, HSP70s also play an important role in facilitating protein-protein interactions, the assembly of multimeric protein complexes, and in the transport of proteins across intracellular membranes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492046&req=5

Figure 1: Functional roles of heat shock proteins (HSP). The evolutionarily conserved molecular chaperones of the HSP70 (HSPA) family fulfill an essential role in maintaining protein quality control in a variety of cell types. Such protective activities center on the ability of the chaperones to assist the correct (re)folding of nascent and denatured proteins, thereby preventing their unwanted aggregation and functional inactivation. However, HSP70s also play an important role in facilitating protein-protein interactions, the assembly of multimeric protein complexes, and in the transport of proteins across intracellular membranes.
Mentions: The 70 kDa HSPs (HSP70) are among the most highly abundant and conserved members of the chaperone family, with at least 13 members represented in the human genome.30 These folding catalysts possess a modular architecture comprising three major functional domains: a conserved N-terminal ATPase domain, a substrate-binding domain and a C-terminal domain that acts as a lid for the substrate binding domain.3435 The substrate binding and release cycle of HSP70s is commonly regulated by co-chaperones from the family of J-domain proteins (primarily HSP40 in eukaryotes) that target these chaperones to their respective substrates, and is further fine-tuned by nucleotide exchange factors.36 The primary function of HSP70s centers on their ability to transiently bind to partially synthesized or denatured peptide sequences, thereby preventing their aggregation and allowing them to (re)fold into a functional state. However, by virtue of their ability to stabilize client proteins in a partially folded state, HSP70s also aid in the transmembrane transport of proteins, and in their assembly into functional complexes35 (Figure 1). A novel, testis-enriched member of this HSP70 family, known as HSPA2, has emerged as a key regulator of several phases of sperm development and maturation.263738

Bottom Line: Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection (ICSI), recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition.While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 (HSPA2), as a key regulator of these events in human spermatozoa.HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization (IVF) success.

View Article: PubMed Central - PubMed

Affiliation: Priority Research Centre in Reproductive Science; Priority Research Centre in Chemical Biology, School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.

ABSTRACT
One of the most common lesions present in the spermatozoa of human infertility patients is an idiopathic failure of sperm-egg recognition. Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection (ICSI), recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition. Previous work in this field has established that the sperm domains responsible for oocyte interaction are formed during spermatogenesis prior to being dynamically modified during epididymal maturation and capacitation in female reproductive tract. While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 (HSPA2), as a key regulator of these events in human spermatozoa. HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization (IVF) success. Furthermore, reduced expression of HSPA2 from the human sperm proteome leads to an impaired capacity for cumulus matrix dispersal, sperm-egg recognition and fertilization following both IVF and ICSI. In this review, we consider the evidence supporting the role of HSPA2 in sperm function and explore the potential mechanisms by which it is depleted in the spermatozoa of infertile patients. Such information offers novel insights into the molecular mechanisms governing sperm function.

No MeSH data available.


Related in: MedlinePlus