Document Type

Open Access Thesis

Embargo Period

8-29-2016

Degree Program

Molecular & Cellular Biology

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2016

Month Degree Awarded

September

Advisor Name

Jennifer

Advisor Last Name

Ross

Co-advisor Name

Thomas

Co-advisor Middle Initial

J

Co-advisor Last Name

Maresca

Third Advisor Name

Peter

Third Advisor Last Name

Chien

Abstract

Understanding how the cellular cytoskeleton is maintained and regulated is important to elucidate the functions of many structures such as the mitotic spindle, cilia and flagella. Katanin p60, microtubule-severing enzymes from the ATPase associated with cellular activities (AAA+) family, has previously been shown in our lab to be inhibited by free tubulin as well as α- and β-tubulin carboxy-terminal tail (CTT) constructs. Here we investigate the inhibition ability of several different tubulin CTT sequences. We quantify the effect of the addition of these constructs on the severing and binding activity of katanin. We find that some constructs inhibit katanin better than others and two constructs that appear to enhance katanin activity. Our findings add nuance to our previous findings that consensus α-tubulin tails are less inhibitory of katanin than consensus β-tubulin [3]. Surprisingly, we find that a polyglutamate sequence activates katanin while it has previously been shown to inhibit spastin, a different microtubule-severing enzyme associated with the neuromuscular disease Hereditary Spastic Paraplegia [23]. These results highlight that different CTT sequences can control the activity of severing enzymes and ultimately affect the cytoskeletal network organization in a cell type and location-dependent manner.

First Advisor

Jennifer Ross

Second Advisor

Thomas Maresca

Third Advisor

Peter Chien

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