Hamzeh, Hussein: Organization and function of signaling molecules in sperm. - Bonn, 2017. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5n-48372
@phdthesis{handle:20.500.11811/7261,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5n-48372,
author = {{Hussein Hamzeh}},
title = {Organization and function of signaling molecules in sperm},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2017,
month = sep,

volume = 00028,
note = {Successful fertilization depends on the ability of sperm to locate the egg. Sperm from different species rely on diverse signaling components to gather chemical and physical cues and transduce them into a behavioral swimming response. External fertilizers like the sea urchin Arbacia punctulata release their gametes into the sea water, where the sperm have to find the egg. Here, the oocyte secretes a chemoattractant – a small peptide called resact. Resact binds to chemoreceptor on sperm flagella, causing an elevation in the intracellular cGMP concentration, which results in a sequence of events that ends with Ca2+ influx. [Ca2+]i modulates sperm flagellar movement, thereby allowing sperm to adjust their swimming direction up the concentration gradient and towards the egg in a process called chemotaxis. A. punctulata sperm are able to register the binding of a single resact molecule; however, the mechanism underlying single-molecule sensitivity and the ensuing cGMP homeostasis are not well understood. Therefore, I first established an in vivo assay to measure cGMP dynamics using reverse opto-chemical engineering (ROCE). My results provide insights into the molecular mechanism how sperm transduce a periodic change in chemoattractant concentration into a periodic change in the asymmetry of the flagellar beat. I also used ROCE to study the single-molecule response in sperm and provide a quantitative description of the molecular events underlying the single-molecule sensitivity in sperm. Moreover, the supra-molecular arrangement of the signaling cascade controlling sperm behavior in sea urchin and mammalian sperm are not known. Therefore, I developed a new labeling strategy to tag the chemoreceptor in sea urchin sperm to elucidate its supra-molecular organization. In mammals, and in particular in human sperm, the “chemoreceptor” is CatSper, the principal Ca2+ channel controlling sperm motility. Using super-resolution microscopy, I unraveled the quadrilateral arrangement of CatSper in mouse and in human sperm.
Before sperm are mature and able to navigate their way to the egg, they have to develop from a round cell into an elongated cell with a head and a tail during spermatogenesis. The non-lysosomal glucosylceramidase GBA2 degrades glucosylceramide (GlcCer) to glucose and ceramide. Lack of GBA2 results in a condition called globozoospermia - manifested with severe morphological defects in mouse sperm. GlcCer accumulation in the absence of GBA2 and the subsequent dysregulation of cytoskeletal dynamics is thought to underlie the defects in sperm shaping during spermatogenesis. I established methods to study the effect of lipid environments on cytoskeletal dynamics to reveal the physiological function of GBA2 during sperm development. My results suggest a novel role for GlcCer as a key regulator for cytoskeletal dynamics during sperm development.},

url = {http://hdl.handle.net/20.500.11811/7261}
}

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