Rab proteins and endocytic trafficking: potential targets for therapeutic intervention.
Rab GTPases serve as master regulators of vesicular membrane transport on both the exo- and endocytic pathways. In their active forms, rab proteins serve in cargo selection and as scaffolds for the sequential assembly of effectors requisite for vesicle budding, cytoskeletal transport, and target membrane fusion. Rab protein function is in turn tightly regulated at the level of protein expression, localization, membrane association, and activation. Alterations in the rab GTPases and associated regulatory proteins or effectors have increasingly been implicated in causing human disease. Some diseases such as those resulting in bleeding and pigmentation disorders (Griscelli syndrome), mental retardation, neuropathy (Charcot-Marie-Tooth), kidney disease (tuberous sclerosis), and blindness (choroideremia) arise from direct loss of function mutations of rab GTPases or associated regulatory molecules. In contrast, in a number of cancers (prostate, liver, breast) as well as vascular, lung, and thyroid diseases, the overexpression of select rab GTPases have been tightly correlated with disease pathogenesis. Unique therapeutic opportunities lie ahead in developing strategies that target rab proteins and modulate the endocytic pathway.
Molecular Trafficking Laboratory, Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Mary-Pat
MP
Stein
Jianbo
J
Dong
Angela
A
Wandinger-Ness
D000818:Animals; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014652:Vascular Diseases / Q000188:drug therapy / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*
D020691:rab GTP-Binding Proteins