Assistant Professor of Cell and Developmental BiologyLab Homepage: http://mcb.berkeley.edu/labs/lishko/
Research in our lab is focused on the cell biology of mammalian fertilization. We study the molecular mechanisms that regulate sperm motility, chemotaxis and the acrosome reaction. A better understanding of these processes will lead to the development of novel approaches to control and preserve male fertility, improve the human reproductive health worldwide and advance family planning.
Co-immunostaining of human spermatozoa with anti-Hv1 antibody (green flagella), anti-COX-IV antibody (red mitochondria) and DAPI (blue nuclei)
Human spermatozoon (a), human sperm flagellum (b) and mouse spermatozoon (c) attached to the recording pipette
On its route to the egg inside the female reproductive tract, mammalian spermatozoa encounter multiple barriers: a viscous cervical mucus, cervical and uterine immune responses, the very narrow lumen of the uterotubal junction, the sticky and extremely complex maze formed by the epithelial folds of the Fallopian tubes, and finally the thick protective glycoprotein envelope (zona pellucida or ZP) of the egg itself. In order to overcome these numerous barriers and eventually fertilize the egg, the sperm cell must sense the cues released by the egg and change its swimming behavior. Sperm can achieve this by increasing the amplitude and driving force of their tail beating, change their direction of movement, and release special enzymes to dissolve the ZP. Such sperm responses depend upon electrical activity of the spermatozoon's plasma membrane which undergoes region-specific changes in ionic permeability in the female reproductive tract. Permeability of the sperm plasma membrane is controlled by ion channels. Ion channels are specialized integral membrane proteins that form ion-conducting pores in normally non-conducting membranes. Ion channels of the sperm cell open in response to environmental cues of the female reproductive tract, thus changing conductance of the sperm plasma membrane and sperm behavior.
The physiological importance of sperm ion channels has inspired numerous attempts to identify and characterize them. However, for about 20 years, these attempts had been frustrated by the inability to apply methods of contemporary biology to the sperm cells due to their small size, specific morphology and vigorous motility. The recently introduced sperm patch clamp technique has, in just a few years, produced a gigantic leap in our understanding of sperm ion channels. We use this method to study sperm ion channels and to shed light on the molecular mechanisms underpinning sperm-egg interaction and the environment of the female reproductive tract during the process of fertilization. This will help us to understand more about the early beginning of life, open new avenues in treatment of male infertility, and create novel male-specific or unisex contraceptives. Below are our on-going projects. Click on the project title to read more about it.
Mannowetz N, Naidoo NM, Choo SA, Smith JF, Lishko PV. Slo1 is the principal potassium channel of human spermatozoa. Elife. 2013 Oct 8;2:e01009. doi: 10.7554/eLife.01009. PMID: 24137539.Smith JF, Syritsyna O, Fellous M, Serres C, Mannowetz N, Kirichok Y, Lishko PV. Disruption of the principal, progesterone-activated sperm Ca2+ channel in a CatSper2-deficient infertile patient. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6823-8. doi: 10.1073/pnas.1216588110. Epub 2013 Mar 25. PMID: 23530196.Lishko P, Clapham DE, Navarro B, Kirichok Y. Sperm patch-clamp. Methods Enzymol. 2013;525:59-83. doi: 10.1016/B978-0-12-397944-5.00004-3. PMID: 23522465.Fedorenko A, Lishko PV, Kirichok Y. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell. 2012 Oct 12;151(2):400-13. doi: 10.1016/j.cell.2012.09.010. PMID: 23063128.Ounjai P, Kim KD, Lishko PV, Downing KH. Three-dimensional structure of the bovine sperm connecting piece revealed by electron cryotomography. Biol Reprod. 2012 Sep 28;87(3):73. Print 2012 Sep. PMID: 22767409.Lishko PV, Kirichok Y, Ren D, Navarro B, Chung JJ, Clapham DE. The control of male fertility by spermatozoan ion channels. Annu Rev Physiol. 2012;74:453-75. doi: 10.1146/annurev-physiol-020911-153258. Epub 2011 Oct 13. PMID: 22017176.Kirichok Y, Lishko PV. Rediscovering sperm ion channels with the patch-clamp technique. Mol Hum Reprod. 2011 Aug;17(8):478-99. doi: 10.1093/molehr/gar044. Epub 2011 Jun 4. PMID: 21642646.Lishko PV, Botchkina IL, Kirichok Y. Progesterone activates the principal Ca2+ channel of human sperm. Nature. 2011 Mar 17;471(7338):387-91. doi: 10.1038/nature09767. PMID: 21412339.Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y. Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel. Cell. 2010 Feb 5;140(3):327-37. doi: 10.1016/j.cell.2009.12.053. PMID: 20144758.Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R. The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron. 2007 Jun 21;54(6):905-18. PMID: 17582331.
Last Updated 2013-11-25