Centrosomes in fertilization, early embryonic development, stem cell division, and cancer

Hoyer‐Fender, Sigrid

doi:10.4267/2042/47311

Cited by 8 publications

(7 citation statements)

References 87 publications

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“…In order to transmit only one centriole during fertilization, sperm of most vertebrates have disintegrated the distal centriole leaving only the proximal centriole. In contrast to centriole reduction in most vertebrates, in mice and other rodents, both distal and proximal centrioles degenerate during spermiogenesis leaving the centriolar vaults (Schatten, 1994; Hoyer-Fender, 2011). The current dogma of centrosome reduction in sperm was recently revisited by investigating the centrosomal protein inventory in human sperm.…”

Section: Discussionmentioning

confidence: 94%

CCDC42 Localizes to Manchette, HTCA and Tail and Interacts With ODF1 and ODF2 in the Formation of the Male Germ Cell Cytoskeleton

Contreras

Hoyer‐Fender

2019

Front. Cell Dev. Biol.

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Terminal differentiation of male germ cells into functional spermatozoa requires shaping and condensation of the nucleus as well as the formation of sperm-specific structures. A transient microtubular structure, the manchette, is mandatory for sperm head shaping and the development of the connecting piece and the sperm tail. The connecting piece or head-to-tail coupling apparatus (HTCA) mediates the tight linkage of sperm head and tail causing decapitation and infertility when faulty. Using mice as the experimental model, several proteins have already been identified affecting the linkage complex, manchette or tail formation when missing. However, our current knowledge is far too rudimentary to even draft an interacting protein network. Depletion of the major outer dense fiber protein 1 (ODF1) mainly caused decapitation and male infertility but validated binding partners collaborating in the formation of sperm-specific structures are largely unknown. Amongst all candidate proteins affecting the HTCA when missing, the structural protein CCDC42 attracted our attention. The coiled-coil domain containing 42 (CCDC42) is important for HTCA and sperm tail formation but is otherwise largely uncharacterized. We show here that CCDC42 is expressed in spermatids and localizes to the manchette, the connecting piece and the tail. Beyond that, we show that CCDC42 is not restricted to male germ cells but is also expressed in somatic cells in which it localizes to the centrosome. Although centrosomal and sperm tail location seems to be irrespective of ODF1 we asked whether both proteins may form an interacting network in the male germ cell. We additionally considered ODF2, a prevalent protein involved in the formation of spermatid-specific cytoskeletal structures, as a putative binding partner. Our data depict for the first time the subcellular location of CCDC42 in spermatids and deepen our knowledge about the composition of the spermatid/sperm-specific structures. The presence of CCDC42 in the centrosome of somatic cells together with the obvious restricted male-specific phenotype when missing strongly argues for a compensatory function by other still unknown proteins most likely of the same family.

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Section: Discussionmentioning

confidence: 94%

CCDC42 Localizes to Manchette, HTCA and Tail and Interacts With ODF1 and ODF2 in the Formation of the Male Germ Cell Cytoskeleton

Contreras

Hoyer‐Fender

2019

Front. Cell Dev. Biol.

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“…This is corroborated by the fact that, in ciliated human cells, C2orf62 is not localized on the cilium itself. Furthermore, in mammalian testis, C2orf62 is not present in mature, flagellate sperm cells, but in spermatocytes and in round and elongating spermatids where flagella formation is initiated [58] . These results suggest that C2orf62 would be important for processes occurring prior to or during cilia formation rather than for cilia maintenance or motility.…”

Section: Discussionmentioning

confidence: 99%

C2orf62 and TTC17 Are Involved in Actin Organization and Ciliogenesis in Zebrafish and Human

et al. 2014

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Vertebrate genomes contain around 20,000 protein-encoding genes, of which a large fraction is still not associated with specific functions. A major task in future genomics will thus be to assign physiological roles to all open reading frames revealed by genome sequencing. Here we show that C2orf62, a highly conserved protein with little homology to characterized proteins, is strongly expressed in testis in zebrafish and mammals, and in various types of ciliated cells during zebrafish development. By yeast two hybrid and GST pull-down, C2orf62 was shown to interact with TTC17, another uncharacterized protein. Depletion of either C2orf62 or TTC17 in human ciliated cells interferes with actin polymerization and reduces the number of primary cilia without changing their length. Zebrafish embryos injected with morpholinos against C2orf62 or TTC17, or with mRNA coding for the C2orf62 C-terminal part containing a RII dimerization/docking (R2D2) – like domain show morphological defects consistent with imperfect ciliogenesis. We provide here the first evidence for a C2orf62-TTC17 axis that would regulate actin polymerization and ciliogenesis.

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“…The centrosome is a conserved organelle located near the center of animal cells that is ∼1‒2 μm in diameter ( Stearns and Winey, 1997 ; Hoyer-Fender, 2012 ). It consists two centrioles characterized by a nine-fold radial arrangement of microtubules surrounded by pericentriolar material (PCM), an ordered structure comprising at least two layers.…”

Section: Introductionmentioning

confidence: 99%

Multifaceted roles of centrosomes in development, health, and disease

Zhou

2021

Journal of Molecular Cell Biology

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The centrosome is a membrane-less organelle consisting of a pair of barrel-shaped centrioles and pericentriolar material and functions as the major microtubule-organizing center and signaling hub in animal cells. The past decades have witnessed the functional complexity and importance of centrosomes in various cellular processes such as cell shaping, division, and migration. In addition, centrosome abnormalities are linked to a wide range of human diseases and pathological states, such as cancer, reproductive disorder, brain disease, and ciliopathies. Herein, we discuss various functions of centrosomes in development and health, with an emphasis on their roles in germ cells, stem cells, and immune responses. We also discuss how centrosome dysfunctions are involved in diseases. A better understanding of the mechanisms regulating centrosome functions may lead the way to potential therapeutic targeting of this organelle in disease treatment.

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Centrosomes in fertilization, early embryonic development, stem cell division, and cancer

Abstract: The centrosome, located at the cell center, is the main microtubule organizing center

Cited by 8 publications

References 87 publications

CCDC42 Localizes to Manchette, HTCA and Tail and Interacts With ODF1 and ODF2 in the Formation of the Male Germ Cell Cytoskeleton

CCDC42 Localizes to Manchette, HTCA and Tail and Interacts With ODF1 and ODF2 in the Formation of the Male Germ Cell Cytoskeleton

C2orf62 and TTC17 Are Involved in Actin Organization and Ciliogenesis in Zebrafish and Human

Multifaceted roles of centrosomes in development, health, and disease

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