Ph.D., California Institute of Technology
Office (501) 526-7418
Lab: (501) 526-7417
Recycling pathways are a key to unraveling the interconnected problems of Golgi apparatus assembly and drug targeting. The Golgi apparatus is the central subcellular organelle within the secretory pathway. Surprisingly, the organized stack structure of Golgi cisternal membranes is dynamically unstable; cisternal Golgi apparatus membrane proteins continuously cycle to the endoplasmic reticulum (ER) and back. Retrograde trafficking from the Golgi apparatus to the ER is independent of any known coat protein and inducible by rab33b, a medial rab protein, and rab6a/6a’, two rab proteins found in the trans Golgi apparatus/trans Golgi network. Rab6a and rab6a’ appear to be redundant to one another while rab33b acts independently of rab6a/a’. Induced Golgi protein recycling to the ER in microtubule-dependent and likely motor protein driven. As revealed by the outcome of an ER-exit block, constitutive Golgi protein recycling is microtubule-independent and little influenced by levels of GDP-restricted rab proteins sufficient to strongly inhibit induced recycling. The recycling of Golgi apparatus proteins to the ER implies that the Golgi apparatus may be evolutionarily a derivative of the ER. In vivio, the Golgi apparatus can assemble de novo from the ER in a staged process in which membrane proteins and matrix dynamically nucleate sites onto which Golgi glycosyltransferases and glycosidases add later. We find the B subunit of Shiga toxin which itself is non-toxic is an effective vector for the delivery of photosensitizers to the Golgi apparatus. Vector delivered photosensitizers are much more effective in cell killing than those delivered by bulk transfer processes. Current work is aimed at characterizing 1) the molecular mechanisms of constitutive and rab induced Golgi protein recycling, 2) the involvement of various gene products in Golgi assembly in vivo, and 3) the potential value of the Golgi apparatus as a target for vector carried photosensitizer delivery.
Garg TK, Szmania SM, Khan JA, Hoering A, Malbrough PA, Moreno-Bost A, Greenway AD, Lingo JD, Li X, Yaccoby S, Suva LJ, Storrie B, Tricot G, Campana D, Shaughnessy Jr JD Jr, Nair BP, Bellamy WT, Epstein J, Barlogie B, van Rhee F., Highly activated and expanded natural killer cells for multiple myeloma immunotherapy. Haematologica. 2012 Mar 14. [Epub ahead of print]. Free Article. Related citations
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