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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005., Includes bibliographical references., BEACH proteins comprise an evolutionarily conserved family characterized by the presence of a BEACH (Beige and Chediak-Higashi) domain of unknown function. They have been shown to play a role in a number of important cellular processes, ranging from cytokinesis to synaptic transmission, and implicated in human diseases, such as Chediak-Higashi Syndrome and cancer. Analysis of several BEACH proteins suggests that they may be involved in membrane trafficking; however, little insight has been gained into their molecular mechanism of function. We identified Drosophila Beach1 in a gain-of-function screen: beach1 overexpression in the photoreceptors drastically alters their growth cone morphology. In a subsequent genetic modifier screen, I identified rabll as a strong enhancer of the beach1 eye overexpression phenotype. Rabll is a small GTPase, which has been shown to regulate the delivery of vesicles and cargo to the plasma membrane via both the recycling and the biosynthetic pathways. Although beach1 loss-of-function mutants exhibit no obvious phenotypes, a sensitized background of a rabll mutant revealed a requirement for beach1 during development and in bristle extension., (cont.) I also found that Beach1 functionally antagonizes Rab11 at the neuromuscular junction by suppressing the rabll synaptic overgrowth phenotype. Subcellular fractionation and double-labeling experiments suggest that these proteins may function in the same subcellular compartment; however, further experiments are needed to determine whether Beach1 and Rab11 interact directly, function in the same protein complex, or closely cooperate in the same molecular pathway. The interaction I found between Beach1 and Rab11 suggests a mechanism by which other BEACH proteins may be involved in vesicle trafficking., by Rita Khodosh., Ph.D.

BEACH proteins comprise an evolutionarily conserved family characterized by the presence of a BEACH (Beige and Chediak-Higashi) domain of unknown function. They have been shown to play a role in a number of important cellular processes, ranging from cytokinesis to synaptic transmission, and implicated in human diseases, such as Chediak-Higashi Syndrome and cancer. Analysis of several BEACH proteins suggests that they may be involved in membrane trafficking; however, little insight has been gained into their molecular mechanism of function. We identified Drosophila Beach1 in a gain-of-function screen: beach1 overexpression in the photoreceptors drastically alters their growth cone morphology. In a subsequent genetic modifier screen, I identified rabll as a strong enhancer of the beach1 eye overexpression phenotype. Rabll is a small GTPase, which has been shown to regulate the delivery of vesicles and cargo to the plasma membrane via both the recycling and the biosynthetic pathways. Although beach1 loss-of-function mutants exhibit no obvious phenotypes, a sensitized background of a rabll mutant revealed a requirement for beach1 during development and in bristle extension., (cont.) I also found that Beach1 functionally antagonizes Rab11 at the neuromuscular junction by suppressing the rabll synaptic overgrowth phenotype. Subcellular fractionation and double-labeling experiments suggest that these proteins may function in the same subcellular compartment; however, further experiments are needed to determine whether Beach1 and Rab11 interact directly, function in the same protein complex, or closely cooperate in the same molecular pathway. The interaction I found between Beach1 and Rab11 suggests a mechanism by which other BEACH proteins may be involved in vesicle trafficking., by Rita Khodosh., Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005., Includes bibliographical references.