No assignee for patent application serial number 499401 has been made.
News editors obtained the following quote from the background information supplied by the inventors: "Cytokinesis is the process by which a single cell separates into two genetically identical daughter cells (8). The events of cytokinesis begin shortly after the sister chromatids separate during mitotic anaphase. As the contractile ring narrows, the future daughter cells are connected by a narrow channel in which the evolutionarily conserved centralspindlin complex (a heterotetrameric complex of MKLP1 and MgcRacGap) localizes (16). Centrosomal 55-kDa protein (CEP55) is recruited from the centrosome to this centrally located complex and interacts with MKLP1 (6, 15, 22). Subsequently, ALIX (ALG-2 interacting protein X, also known as programmed cell death 6 interacting protein) and TSG101 (a component of the ESCRT-1 [endosomal sorting complex required for transport-1] complex) are recruited to the midbody through coiled-coil interactions with the CEP55 homodimer (3, 15, 17). Glycine (G)-proline (P)-proline (P)--X--XX-tyrosine (Y) (GPPX3Y) motifs in ALIX and TSG101 are critical for this interaction with CEP55 (14, 17). Knockdown experiments in somatic cells have revealed that a deficiency of CEP55 leads to incomplete abscission and formation of multinucleated cells (3, 17). In addition, knockdown of either TSG101 or ALIX, known direct downstream interacting partners of CEP55, leads to a similar phenotype (3, 17). These interactions are essential for somatic cell abscission (2, 3, 17).
"In contrast to these abscission events in somatic cells, differentiating germ cells do not complete cytokinesis and instead are linked together through 0.5- to 3-.quadrature.m electron-dense 'channels' called intercellular bridges (5, 7, 12). Intercellular bridges are evolutionarily conserved structures that are present in the gonads of essentially all multicellular organisms from fruit flies and hydra to marsupials, mice, and humans. In mammals, intercellular bridges play roles in synchronization of germ cells by passage of organelles and molecules between germ cells (especially important postmeiotically in haploid spermatids) (1, 19).
"It has been previously shown that testis expressed gene 14 (TEX14) localizes to male and female germ cell intercellular bridges (9, 11) and that the bridge forms through a direct interaction between TEX14 and the MKLP1-containing midbody protein complex (10). TEX14-positive intercellular bridges interconnect human and mouse spermatogonia as soon as spermatogonia begin to differentiate and continue to interconnect male germ cells up through formation of mature spermatozoa (11). Targeted deletion of TEX14 disrupts intercellular bridges in germ cells and causes sterility in male mice (11) but not in female mice (9). Furthermore, not only do MKLP1 and TEX14 interact in male germ cells, but MKLP1 and its centralspindlin complex partner, MgcRacGap, become stable components of the intercellular bridge (10). These results demonstrate that intercellular bridges are essential for spermatogenesis; however, until now, it was unclear how TEX14 participated in intercellular bridge formation to prevent abscission and the completion of cytokinesis in male germ cells. We demonstrate here that a TEX14-CEP55 interaction is critical for subverting abscission toward a stable intercellular bridge."
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