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Temporal coordination of meiosis with spermatid morphogenesis is crucial for successful generation of mature sperm cells. We identified a recessive male sterile Drosophila melanogaster mutant, mitoshell, in which events of spermatid morphogenesis are initiated too early, before meiotic onset. Premature mitochondrial aggregation and fusion lead to an aberrant mitochondrial shell around premeiotic nuclei. Despite successful meiotic karyokinesis, improper mitochondrial localization in mitoshell testes is associated with defective astral central spindles and a lack of contractile rings, leading to meiotic cytokinesis failure. We mapped and cloned the mitoshell gene and found that it encodes a novel protein with a bromodomain-related region. It is conserved in some insect lineages. Bromodomains typically bind to histone acetyl-lysine residues and therefore are often associated with chromatin. The Mitoshell bromodomain-related region is predicted to have an alpha helical structure similar to that of bromodomains, but not all the crucial residues in the ligand-binding loops are conserved. We speculate that Mitoshell may participate in transcriptional regulation of spermatogenesis-specific genes, though perhaps with different ligand specificity compared to traditional bromodomains.

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Thrombin bound to endothelial thrombomodulin (TM) activates protein C (PC) into activated protein C (APC) with the aid of endothelial protein C receptor (EPCR). We determined if TM and EPCR are also expressed in PC‐3 and DU‐145 prostate cancer (CaP) cell lines, their ability to activate PC into APC, and how each of the proteins involved in this system regulates CaP cell proliferation and invasion. Real‐Time PCR, Western Blotting, and confocal microscopy demonstrated that TM and EPCR are expressed by both cell lines and both cell lines activated PC into APC in the presence of thrombin. PC, APC, and thrombin alone did not affect CaP cell proliferation or invasion. Since APC affects ovarian tumor cell invasion by competing with urokinase type plasminogen activator (uPA) for binding to plasminogen activator inhibitor‐I (PAI‐1), we determined if APC also regulates CaP invasion. APC competed with uPA for binding to PAI‐1 in CaP cells, enabling uPA to increase DU‐145 invasion. We conclude that the CaP cells make TM and EPCR and generate APC. Although PC, APC, and thrombin alone do not affect CaP cell proliferation or invasion, in the presence of CaP cell TM and EPCR and exogenously added thrombin, PC, PAI‐1 and uPA, APC is generated and binds to PAI‐1, freeing uPA to facilitate CaP tumor cell invasion.This research was made possible by NIH Grant Number P20 RR‐016461, the McKay Urology Endowment Fund, and the Hemby Foundation.

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