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Manipulation of the host cell plasma membrane is critical during infection by intracellular bacterial pathogens, particularly during bacterial entry into and exit from host cells. To manipulate host cells, bacteria deploy secreted proteins that modulate or modify host cell components. Here, we review recent advances that suggest common themes by which bacteria manipulate the host cell plasma membrane. One theme is that bacteria use diverse strategies to target or influence host cell plasma membrane composition and shape. A second theme is that bacteria take advantage of host cell plasma membrane-associated pathways such as signal transduction, endocytosis, and exocytosis. Future investigation into how bacterial and host factors contribute to plasma membrane manipulation by bacterial pathogens will reveal new insights into pathogenesis and fundamental principles of plasma membrane biology.

CHK-2 kinase is a master regulator of meiosis in C. elegans. Its activity is required for homolog pairing and synapsis and for double-strand break formation, but how it drives and coordinates these pathways to ensure crossover formation remains unknown. Here we show that CHK-2 promotes pairing and synapsis by phosphorylating a family of zinc finger proteins that bind to specialized regions on each chromosome known as pairing centers, priming their recruitment of the Polo-like kinase PLK-2. This knowledge enabled the development of a phospho-specific antibody as a tool to monitor CHK-2 activity. When either synapsis or crossover formation is impaired, CHK-2 activity is prolonged, and meiotic progression is delayed. We show that this common feedback circuit is mediated by interactions among a network of HORMA domain proteins within the chromosome axis and generates a graded signal. These findings reveal conserved regulatory mechanisms that ensure faithful meiotic chromosome segregation in diverse species.

Proteins of the HORMA domain family play central, but poorly understood, roles in chromosome organization and dynamics during meiosis. In Caenorhabditis elegans, four such proteins (HIM-3, HTP-1, HTP-2, and HTP-3) have distinct but overlapping functions. Through combined biochemical, structural, and in vivo analysis, we find that these proteins form hierarchical complexes through binding of their HORMA domains to cognate peptides within their partners' C-terminal tails, analogous to the "safety belt" binding mechanism of Mad2. These interactions are critical for recruitment of HIM-3, HTP-1, and HTP-2 to chromosome axes. HTP-3, in addition to recruiting the other HORMA domain proteins to the axis, plays an independent role in sister chromatid cohesion and double-strand break formation. Finally, we find that mammalian HORMAD1 binds a motif found both at its own C terminus and at that of HORMAD2, indicating that this mode of intermolecular association is a conserved feature of meiotic chromosome structure in eukaryotes.