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Putting things in place for fertilization: discovering roles for importin proteins in cell fate and spermatogenesis.

Loveland KL, Major AT, Butler R, Young JC, Jans DA, Miyamoto Y - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: Knowledge of importin function has expanded substantially in regard to three key developmental systems: embryonic stem cells, muscle cells and the germ line.In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate.These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, including via directing proteins to distinct intracellular compartments and by determining cellular stress responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology;Department of Anatomy and Developmental Biology, Monash University; Hudson Institute of Medical Research, Monash Medical Centre; School of Clinical Sciences, Monash University, Clayton, VIC, Australia, .

ABSTRACT
Importin proteins were originally characterized for their central role in protein transport through the nuclear pores, the only intracellular entry to the nucleus. This vital function must be tightly regulated to control access by transcription factors and other nuclear proteins to genomic DNA, to achieve appropriate modulation of cellular behaviors affecting cell fate. Importin-mediated nucleocytoplasmic transport relies on their specific recognition of cargoes, with each importin binding to distinct and overlapping protein subsets. Knowledge of importin function has expanded substantially in regard to three key developmental systems: embryonic stem cells, muscle cells and the germ line. In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate. This review presents key findings from studies of mammalian spermatogenesis that reveal potential new pathways by which male fertility and infertility arise. These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, including via directing proteins to distinct intracellular compartments and by determining cellular stress responses.

No MeSH data available.


Related in: MedlinePlus

Importins contribute to many stages of mammalian sperm formation. (a) Importin α2 protein is present in mature mouse spermatozoa. Detection of importin α2 in sperm isolated from the mouse cauda epididymis using direct immunofluorescence revealed that it is localized predominantly to the anterior region of the acrosome, with additional signals detected most readily in the principle piece of the tail. (b) Schematic illustration of phases of spermatogenesis in which distinct roles for importin proteins have been identified or postulated through the studies outlined in this review. The established role in nucleocytoplasmic transport is likely to function at all stages. The presence of nuclear-localized importins α2 and α4 suggests that they have a role in physiological processes related to cellular stress behaviors in post-mitotic male germline cells. The contribution of importins to formation of the acrosome and other subcellular domains in the highly organized mature spermatid is evident from published and ongoing work.
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Figure 4: Importins contribute to many stages of mammalian sperm formation. (a) Importin α2 protein is present in mature mouse spermatozoa. Detection of importin α2 in sperm isolated from the mouse cauda epididymis using direct immunofluorescence revealed that it is localized predominantly to the anterior region of the acrosome, with additional signals detected most readily in the principle piece of the tail. (b) Schematic illustration of phases of spermatogenesis in which distinct roles for importin proteins have been identified or postulated through the studies outlined in this review. The established role in nucleocytoplasmic transport is likely to function at all stages. The presence of nuclear-localized importins α2 and α4 suggests that they have a role in physiological processes related to cellular stress behaviors in post-mitotic male germline cells. The contribution of importins to formation of the acrosome and other subcellular domains in the highly organized mature spermatid is evident from published and ongoing work.

Mentions: As highlighted in previous sections, there is increasing evidence that importins contribute to the formation of distinct subcellular domains in both the nucleus and cytoplasm. In addition to the discovery that importin α6 is associated with the developing acrosome, our preliminary indirect immunofluorescence analyses suggest that each importin localizes to a discrete region in epididymal mouse spermatozoa (Figure 4a), and several independent proteomic analyses have shown that importins are present in post-testicular germ cells (e.g.,48). It remains to be established whether importins play active roles in delivering proteins to the correct domain, whether they merely restrict their movements between different compartments by binding to them, and whether they are integral to the formation of intracellular complex formations by serving as molecular scaffolds.


Putting things in place for fertilization: discovering roles for importin proteins in cell fate and spermatogenesis.

Loveland KL, Major AT, Butler R, Young JC, Jans DA, Miyamoto Y - Asian J. Androl. (2015 Jul-Aug)

Importins contribute to many stages of mammalian sperm formation. (a) Importin α2 protein is present in mature mouse spermatozoa. Detection of importin α2 in sperm isolated from the mouse cauda epididymis using direct immunofluorescence revealed that it is localized predominantly to the anterior region of the acrosome, with additional signals detected most readily in the principle piece of the tail. (b) Schematic illustration of phases of spermatogenesis in which distinct roles for importin proteins have been identified or postulated through the studies outlined in this review. The established role in nucleocytoplasmic transport is likely to function at all stages. The presence of nuclear-localized importins α2 and α4 suggests that they have a role in physiological processes related to cellular stress behaviors in post-mitotic male germline cells. The contribution of importins to formation of the acrosome and other subcellular domains in the highly organized mature spermatid is evident from published and ongoing work.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492042&req=5

Figure 4: Importins contribute to many stages of mammalian sperm formation. (a) Importin α2 protein is present in mature mouse spermatozoa. Detection of importin α2 in sperm isolated from the mouse cauda epididymis using direct immunofluorescence revealed that it is localized predominantly to the anterior region of the acrosome, with additional signals detected most readily in the principle piece of the tail. (b) Schematic illustration of phases of spermatogenesis in which distinct roles for importin proteins have been identified or postulated through the studies outlined in this review. The established role in nucleocytoplasmic transport is likely to function at all stages. The presence of nuclear-localized importins α2 and α4 suggests that they have a role in physiological processes related to cellular stress behaviors in post-mitotic male germline cells. The contribution of importins to formation of the acrosome and other subcellular domains in the highly organized mature spermatid is evident from published and ongoing work.
Mentions: As highlighted in previous sections, there is increasing evidence that importins contribute to the formation of distinct subcellular domains in both the nucleus and cytoplasm. In addition to the discovery that importin α6 is associated with the developing acrosome, our preliminary indirect immunofluorescence analyses suggest that each importin localizes to a discrete region in epididymal mouse spermatozoa (Figure 4a), and several independent proteomic analyses have shown that importins are present in post-testicular germ cells (e.g.,48). It remains to be established whether importins play active roles in delivering proteins to the correct domain, whether they merely restrict their movements between different compartments by binding to them, and whether they are integral to the formation of intracellular complex formations by serving as molecular scaffolds.

Bottom Line: Knowledge of importin function has expanded substantially in regard to three key developmental systems: embryonic stem cells, muscle cells and the germ line.In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate.These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, including via directing proteins to distinct intracellular compartments and by determining cellular stress responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology;Department of Anatomy and Developmental Biology, Monash University; Hudson Institute of Medical Research, Monash Medical Centre; School of Clinical Sciences, Monash University, Clayton, VIC, Australia, .

ABSTRACT
Importin proteins were originally characterized for their central role in protein transport through the nuclear pores, the only intracellular entry to the nucleus. This vital function must be tightly regulated to control access by transcription factors and other nuclear proteins to genomic DNA, to achieve appropriate modulation of cellular behaviors affecting cell fate. Importin-mediated nucleocytoplasmic transport relies on their specific recognition of cargoes, with each importin binding to distinct and overlapping protein subsets. Knowledge of importin function has expanded substantially in regard to three key developmental systems: embryonic stem cells, muscle cells and the germ line. In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate. This review presents key findings from studies of mammalian spermatogenesis that reveal potential new pathways by which male fertility and infertility arise. These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, including via directing proteins to distinct intracellular compartments and by determining cellular stress responses.

No MeSH data available.


Related in: MedlinePlus