Dynein independent roles for dynein light chain in meiotic progression

Emory University, Atlanta GA

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Abstract

Project Summary Homologous chromosome pairing and meiotic synapsis are essential processes that are required in both oogenesis and spermatogenesis to prevent aneuploidy and developmental defects in offspring. Despite the importance and high conservation of synapsis, not every aspect is the same between the two sexes. Heterogametic species have evolved less stringent or differential regulation of meiotic pairing and synapsis in order to successfully pass on their genetic information. My preliminary results indicate that male and female C. elegans even have different requirements for dynein in regulating the initiation of synapsis. Dynein dependent forces have been proposed to test that a potential homolog match is correct, and once this has been established, synapsis (SYP) protein loading between the homologs initiates. Knockdown of the dynein light chain (DLC-1) at an elevated temperature results in SYP polycomplex formation away from chromatin in females. Unexpectedly, DLC-1 depletion in males at the same temperature shows grossly normal synapsis. Even more surprisingly, mutants in the heavy chain and dynactin components of dynein also do not show SYP polycomplexes in female meiosis. This indicates that there is a previously undescribed function for DLC-1 in synapsis initiation. There are many examples of dynein-independent functions for DLC-1, including stabilizing or interrupting dimer interactions. A consensus binding motif for the DLC-1 ortholog has been reported, and there is a potential binding motif in one of the SYP proteins. I hypothesize that DLC-1 functions to regulate SYP protein interactions until correct pairing has been verified. I further hypothesize that males employ an alternative method to regulate synapsis initiation. Specific Aim I investigates the role that DLC-1 has in female meiosis by testing if it interacts directly with synapsis proteins, and DLC-1 interactors in female meiosis will be identified and tested for a role in synapsis initiation. Specific Aim II focuses on why males do not require DLC-1 by assessing if males need dynein at all in pairing chromosomes, and investigate whether a redundancy in light chains evolved in male meiosis. Understanding such sex specific differences in meiotic regulation using a genetically tractable organism will help us better understand natural and disease states in humans that lead to an increased incidence of aneuploidy and meiotically based infertility.