Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions

Wei Zhou, Simone J. Stanger, Amanda L. Anderson, Ilana R. Bernstein, Geoffry N. De Iuliis, Adam McCluskey, Eileen A. McLaughlin, Matthew D. Dun, Brett Nixon

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Abstract

Background: The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored in preparation for ejaculation. Making important contributions to both processes are epididymosomes, small extracellular vesicles released from the epididymal soma via an apocrine secretory pathway. While considerable effort has been focused on defining the cargo transferred between epididymosomes and spermatozoa, comparatively less is known about the mechanistic basis of these interactions. To investigate this phenomenon, we have utilized an in vitro co-culture system to track the transfer of biotinylated protein cargo between mouse epididymosomes and recipient spermatozoa isolated from the caput epididymis; an epididymal segment that is of critical importance for promoting sperm maturation. Results: Our data indicate that epididymosome-sperm interactions are initiated via tethering of the epididymosome to receptors restricted to the post-acrosomal domain of the sperm head. Thereafter, epididymosomes mediate the transfer of protein cargo to spermatozoa via a process that is dependent on dynamin, a family of mechanoenzymes that direct intercellular vesicle trafficking. Notably, upon co-culture of sperm with epididymosomes, dynamin 1 undergoes a pronounced relocation between the peri- and post-acrosomal domains of the sperm head. This repositioning of dynamin 1 is potentially mediated via its association with membrane rafts and ideally locates the enzyme to facilitate the uptake of epididymosome-borne proteins. Accordingly, disruption of membrane raft integrity or pharmacological inhibition of dynamin both potently suppress the transfer of biotinylated epididymosome proteins to spermatozoa. Conclusion: Together, these data provide new mechanistic insight into epididymosome-sperm interactions with potential implications extending to the manipulation of sperm maturation for the purpose of fertility regulation.

Original languageEnglish
Article number35
Pages (from-to)1-18
Number of pages18
JournalBMC Biology
Volume17
Issue number1
DOIs
Publication statusPublished - 18 Apr 2019

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cargo
sperm
Spermatozoa
Dynamin I
spermatozoa
Dynamins
Proteins
Sperm Maturation
protein
Membranes
Sperm Head
Relocation
vesicle
Epididymis
Carisoprodol
Coculture Techniques
maturation
membrane
epididymis
trafficking

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Zhou, W., Stanger, S. J., Anderson, A. L., Bernstein, I. R., De Iuliis, G. N., McCluskey, A., ... Nixon, B. (2019). Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions. BMC Biology, 17(1), 1-18. [35]. https://doi.org/10.1186/s12915-019-0653-5
Zhou, Wei ; Stanger, Simone J. ; Anderson, Amanda L. ; Bernstein, Ilana R. ; De Iuliis, Geoffry N. ; McCluskey, Adam ; McLaughlin, Eileen A. ; Dun, Matthew D. ; Nixon, Brett. / Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions. In: BMC Biology. 2019 ; Vol. 17, No. 1. pp. 1-18.
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Zhou, W, Stanger, SJ, Anderson, AL, Bernstein, IR, De Iuliis, GN, McCluskey, A, McLaughlin, EA, Dun, MD & Nixon, B 2019, 'Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions', BMC Biology, vol. 17, no. 1, 35, pp. 1-18. https://doi.org/10.1186/s12915-019-0653-5

Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions. / Zhou, Wei; Stanger, Simone J.; Anderson, Amanda L.; Bernstein, Ilana R.; De Iuliis, Geoffry N.; McCluskey, Adam; McLaughlin, Eileen A.; Dun, Matthew D.; Nixon, Brett.

In: BMC Biology, Vol. 17, No. 1, 35, 18.04.2019, p. 1-18.

Research output: Contribution to journalArticle

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T1 - Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions

AU - Zhou, Wei

AU - Stanger, Simone J.

AU - Anderson, Amanda L.

AU - Bernstein, Ilana R.

AU - De Iuliis, Geoffry N.

AU - McCluskey, Adam

AU - McLaughlin, Eileen A.

AU - Dun, Matthew D.

AU - Nixon, Brett

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N2 - Background: The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored in preparation for ejaculation. Making important contributions to both processes are epididymosomes, small extracellular vesicles released from the epididymal soma via an apocrine secretory pathway. While considerable effort has been focused on defining the cargo transferred between epididymosomes and spermatozoa, comparatively less is known about the mechanistic basis of these interactions. To investigate this phenomenon, we have utilized an in vitro co-culture system to track the transfer of biotinylated protein cargo between mouse epididymosomes and recipient spermatozoa isolated from the caput epididymis; an epididymal segment that is of critical importance for promoting sperm maturation. Results: Our data indicate that epididymosome-sperm interactions are initiated via tethering of the epididymosome to receptors restricted to the post-acrosomal domain of the sperm head. Thereafter, epididymosomes mediate the transfer of protein cargo to spermatozoa via a process that is dependent on dynamin, a family of mechanoenzymes that direct intercellular vesicle trafficking. Notably, upon co-culture of sperm with epididymosomes, dynamin 1 undergoes a pronounced relocation between the peri- and post-acrosomal domains of the sperm head. This repositioning of dynamin 1 is potentially mediated via its association with membrane rafts and ideally locates the enzyme to facilitate the uptake of epididymosome-borne proteins. Accordingly, disruption of membrane raft integrity or pharmacological inhibition of dynamin both potently suppress the transfer of biotinylated epididymosome proteins to spermatozoa. Conclusion: Together, these data provide new mechanistic insight into epididymosome-sperm interactions with potential implications extending to the manipulation of sperm maturation for the purpose of fertility regulation.

AB - Background: The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored in preparation for ejaculation. Making important contributions to both processes are epididymosomes, small extracellular vesicles released from the epididymal soma via an apocrine secretory pathway. While considerable effort has been focused on defining the cargo transferred between epididymosomes and spermatozoa, comparatively less is known about the mechanistic basis of these interactions. To investigate this phenomenon, we have utilized an in vitro co-culture system to track the transfer of biotinylated protein cargo between mouse epididymosomes and recipient spermatozoa isolated from the caput epididymis; an epididymal segment that is of critical importance for promoting sperm maturation. Results: Our data indicate that epididymosome-sperm interactions are initiated via tethering of the epididymosome to receptors restricted to the post-acrosomal domain of the sperm head. Thereafter, epididymosomes mediate the transfer of protein cargo to spermatozoa via a process that is dependent on dynamin, a family of mechanoenzymes that direct intercellular vesicle trafficking. Notably, upon co-culture of sperm with epididymosomes, dynamin 1 undergoes a pronounced relocation between the peri- and post-acrosomal domains of the sperm head. This repositioning of dynamin 1 is potentially mediated via its association with membrane rafts and ideally locates the enzyme to facilitate the uptake of epididymosome-borne proteins. Accordingly, disruption of membrane raft integrity or pharmacological inhibition of dynamin both potently suppress the transfer of biotinylated epididymosome proteins to spermatozoa. Conclusion: Together, these data provide new mechanistic insight into epididymosome-sperm interactions with potential implications extending to the manipulation of sperm maturation for the purpose of fertility regulation.

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Zhou W, Stanger SJ, Anderson AL, Bernstein IR, De Iuliis GN, McCluskey A et al. Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions. BMC Biology. 2019 Apr 18;17(1):1-18. 35. https://doi.org/10.1186/s12915-019-0653-5