Advisor(s)

Erin J. Cram

Contributor(s)

William H. Ahearn, Veronica S. Godoy-Carter

Date of Award

2010

Date Accepted

12-2010

Degree Grantor

Northeastern University

Degree Level

M.S.

Degree Name

Master of Science

Department or Academic Unit

College of Arts and Sciences. Department of Biology.

Keywords

C. elegans, filamin, biochemical, gene structure

Subject Categories

Caenorhabditis elegans - Phylogeny, Genetic code, Biochemical genetics

Disciplines

Genetics and Genomics

Abstract

Filamins are long, flexible, multi-domain proteins composed of an N-terminal actin-binding domain (ABD) followed by multiple immunoglobulin-like repeats (Ig-FLN). They function to anchor, organize and maintain the actin cytoskeleton, to provide scaffolds for signaling components, and to act as sensors for mechanical forces. In this study, we use a cDNA sequencing and bioinformatics approach to identify and describe the gene structure, expression patterns and phylogeny of the C. elegans filamin orthologs encoded by fln-1 and fln-2. We also used homology modeling to predict the protein structures. Our results reveal that C. elegans FLN-1 is well conserved at the sequence level with respect to vertebrate filamins, particularly in the ABD and several key Ig-FLN repeats. The domain organization of C. elegans FLN-1 is quite similar to filamins in humans and other organisms. FLN-2 is more divergent, with more than 23 Ig-FLN repeats interspersed among large regions that do not appear in other known filamins. Nevertheless, we demonstrated that FLN-2 binds actin and plays a role in cell attachment and cell migration in vivo. Knockdown by RNA interference of fln-2 results in defects in molting and cuticle attachment, tail morphogenesis, and distal tip cell (DTC) migration, which suggest that FLN-2 plays an important role in these processes. Our results help inform and validate future genetic and biochemical studies of filamin function, particularly those using C. elegans as a model system.

Document Type

Master's Thesis

Rights Holder

Christina DeMaso


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