Undergraduate Honors Theses

Thesis Defended

Spring 2017

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Prof. Dr. Ding Xue

Second Advisor

Dr. Eui Seung Lee

Third Advisor

Assoc. Prof. Dr. Christopher Link

Fourth Advisor

Dr. Christy Fillman

Abstract

Programmed cell death plays a major physiological role in cell elimination in order to maintain cell homeostasis. Cell engulfment and clearance are important final steps of programmed cell death. Apoptotic cell clearance in C.elegans is triggered by alteration in phospholipid asymmetry. Phosphatidylserine (PS), which exists in the inner leaflet of plasma membrane in dormant cells, is externalized onto the outer leaflet during apoptosis and signals phagocytic cells for engulfment. PSR-1(PS Receptor) in C.elegans has been shown as a protein that preferentially binds to PS. PSR-1 was first discovered as a transmembrane protein on phagocytes that engulf apoptotic cells; with the N-terminal region in the cytosol and the C-terminal region in the extracellular space. This implies that the primary function of detecting externalized PS might be performed by the C-terminal portion of the protein. Therefore, single and double mutants of psr-1 C-terminal domain were generated with ced-1, ced-8 and acced-8(sm351). The C-terminal region of psr-1 was found to play an important role in maintaining a regulated cell clearance mechanism. Both versions of psr-1 C-terminal region mutants exhibited an increased cell clearance phenotype. Depending on the length of deletion at C-terminus, the two psr-1 mutants showed different numbers of somatic cell corpse in each embryonic stage when ced-8 was activated (acCED-8).While acced-8(sm351) mutant alone exhibited N2-like phenotype, double mutants of psr-1 with acced-8(sm351) exhibited significantly different phenotype when compared to one another. This observation strongly indicates that PSR-1 C-terminal region is critical for cell corpse clearance in coordination with acCED-8.

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