Mammalian spermiogenesis and the formation of the sperm head to tail coupling apparatus

by Constanza Tapia Contreras
Doctoral thesis
Date of Examination:2021-05-18
Date of issue:2021-08-24
Advisor:Prof. Dr. Sigrid Hoyer-Fender
Referee:Prof. Dr. Sigrid Hoyer-Fender
Referee:Prof. Dr. Rüdiger Behr
Referee:Prof. Dr. Ernst A. Wimmer
Referee:Dr. Melina Schuh
Referee:Prof. Dr. Hubertus Jarry
Referee:Prof. Dr. Peter Burfeind
Persistent Address: http://dx.doi.org/10.53846/goediss-8793

 

 

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Abstract

English

The head-tail coupling apparatus (HTCA), also known as connecting piece, provides the physical linkage between the sperm head and its tail. The HTCA morphogenesis initiates during spermiogenesis and is assembled at the posterior area of the spermatid nucleus. The HTCA is built around the proximal and the distal centriole, and consists of the accessory structures, basal plate, capitulum, and segmented columns. These structures are responsible for the tight attachment of the sperm head to the tail, and their disruption leads to acephalic spermatozoa syndrome and male infertility. Thus, the stable connection is essential for moving the sperm nucleus towards the oocyte and successful fertilization. However, its molecular composition is scarcely known. The outer dense fiber protein 1 (ODF1) is a component of the HTCA and involved in the tight junction of the sperm head to the tail. Odf1 depletion as well as the partial disruption of Hook1 and Spag4l cause sperm decapitation and male infertility in mice. In humans, however, mutations in these genes remain largely unknown. Thus, the DNA from two patients with the acephalic spermatozoa syndrome was screened for mutations. The screen performed in this study reveals a normal Odf1 gene sequence. Besides, exons 10 and 11 of Hook1 and exons 6 and 8 of Spag4l were identical to the wild type variant. Therefore, the analyzed regions of the genes Odf1, Hook1, and Spag4l seem not to be implicated in the acephalic syndrome suffered by the two patients here studied. Beyond that, the interaction between ODF1 and the nuclear membrane protein SPAG4 has been reported as a novel male germ cell-specific linkage complex between the cytoskeletal connecting piece and the nuclear membrane, although their mechanism of interaction is unclear. Thus, the induction of dimerization by rapamycin was explored as a new tool to analyze SUN4 and SUN5 topology. Besides ODF1 or SPAG4 interacting proteins that collaborate in the formation of the HTCA have not been identified. In this study, the coiled-coil domain containing 42 (CCDC42), another essential HTCA component that causes decapitation when missing, and the cilia and flagella associated protein 52 (CFAP52) have been characterized in detail. CCDC42 has been localized to the manchette, perinuclear ring, and tail in male germ cells. CCDC42 interacts biochemically with the outer dense fiber proteins ODF1 and ODF2. These interactions might contribute to the assembly of proteins required for the formation and the stability of the HTCA. CFAP52 localizes to the manchette and sperm tail, indicating that CFAP52 is another promising candidate for the HTCA interacting network.
Keywords: HTCA, CCDC42, CFAP52, acephalic spermatozoa syndrome, male infertility
 
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