The role of the cytoskeleton in germ cell apoptosis in C. elegans

Fred Hutchinson Cancer Research Center, Seattle WA

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Abstract

DESCRIPTION (provided by applicant): Programmed cell death or apoptosis is a fundamental, highly conserved pathway in animal development, and plays critical roles in normal health, as well as in aging and disease. Apoptotic cells must shut themselves down while leaving surrounding cells and tissues intact, and part of this process involves changes in the cytoskeleton of the apoptotic cells. Studies in the genetic model system C. elegans identified many of the key molecules that regulate and execute apoptosis, and this grant uses C. elegans as a system to understand the apoptotic regulation of the microtubule cytoskeleton. The study focuses on adult gonads, where about 50% of germ cells normally undergo apoptosis. The gonad is an example of a syncytial tissue, where individual cells maintain small cytoplasmic connections with neighboring cells. In a syncytium, the apoptotic removal of nuclei and cytoplasm must be tightly controlled to prevent death of the whole. The connections between cells present the possibility that part or all of the apoptotic cytoplasm might be transferred intact to the syncytium, rather than simply being degraded and recycled as metabolites. This grant examines how the normal microtubule cytoskeleton is dismantled during germ cell apoptosis, and how the new cytoskeleton is organized. It addresses the fate of cytoplasmc components of the apoptotic cell, and whether the new MT cytoskeleton contributes to the transfer of cytoplasm. Through either transfer or digestion, the apoptotic cell ultimately shrinks its cytoplasm, dismantles its cytoskeleton entirely, and is absorbed by other cells. This study identifies a role for the conserved kinase PAR-1 in the final steps of apoptotic remodeling, and addresses possible steps that might be regulated by PAR-1 activity.