The author of this document has limited its availability to on-campus or logged-in CSUSB users only.

Off-campus CSUSB users: To download restricted items, please log in to our proxy server with your MyCoyote username and password.

Date of Award


Document Type

Restricted Thesis: Campus only access

Degree Name

Master of Science in Biology



First Reader/Committee Chair

Daniel Nickerson


Eukaryotic cells maintain integrity and biochemical functions of discrete organelles using a network of vesicular trafficking pathways regulated by lipid-anchored Rab GTPase signaling proteins (Rabs). Rabs control where and when vesicles fuse with target membranes, ensuring appropriate cargo (proteins, lipids, etc.) delivery. Controlled cycling between active and inactive conformations is important for Rabs to properly regulate traffic. In their active conformation Rabs can localize to a client membrane, interact with tethering and membrane fusion proteins, which will facilitate membrane fusion. Regulation of Rabs is dependent upon GTPase accelerating proteins (GAPs). GAPs trigger GTP hydrolysis and return the Rab to its GDP-bound, inactive state. Rab GAPs are important to maintain the efficiency and fidelity of transport pathways. Rab GAPs with defects in functionality are implicated in a variety of human diseases. Rab GAPs tend to be cytosolic proteins that transiently localize to membranes to survey for their client Rab. We report that the evolutionarily conserved yeast Rab GAP Gyp8 is an atypical Rab GAP containing a transmembrane domain at its C-terminus. Gyp8 bears structural similarity to tail-anchored (TA) proteins, follows a transport itinerary similar to many yeast TA proteins, and depends upon molecular machinery specialized for regulation of TA protein localization. We report mechanisms that regulate delivery of Gyp8 to mitochondrion, ER and peroxisomes.