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Vol. 14, Issue 2, 698-720, February 2003

Mammalian Ykt6 Is a Neuronal SNARE Targeted to a Specialized Compartment by its Profilin-like Amino Terminal Domain

Haruki Hasegawa,^* Sara Zinsser,^* Yeyoung Rhee,^* Einar Osland Vik-Mo, Svend Davanger, and Jesse C. Hay^*

 ^*University of Michigan, Department of Molecular, Cellular, and Developmental Biology, Ann Arbor, Michigan 48109-1048; and  University of Bergen, Department of Anatomy and Cell Biology, and Locus on Neuroscience, Bergen, Norway

SNAREs are required for specific membrane fusion throughout the endomembrane system. Here we report the characterization of rat ykt6, a prenylated SNARE selectively expressed in brain neurons. Immunofluorescence microscopy in neuronal and neuroendocrine cell lines revealed that membrane-associated ykt6 did not colocalize significantly with any conventional markers of endosomes, lysosomes, or the secretory pathway. However, ykt6-containing membranes displayed very minor overlaps with lysosomes and dense-core secretory granules and were similar to lysosomes in buoyant density. Thus, ykt6 appears to be specialized for the trafficking of a unique membrane compartment, perhaps related to lysosomes, involved in aspects of neuronal function. Targeting of this SNARE to the ykt6 compartment was mediated by its profilin-like amino-terminal domain, even in the absence of protein prenylation. Although several other R-SNAREs contain related amino-terminal domains, only the ykt6 version was able to confer the specialized localization. Rat ykt6, which contains an arginine in its SNARE motif zero-layer, was found to behave like other R-SNAREs in its SNARE assembly properties. Interestingly, cytosolic ykt6, constituting more than half of the total cellular pool, appeared to be conformationally inactive for SNARE complex assembly, perhaps indicative of a regulatory mechanism that prevents promiscuous and potentially deleterious SNARE interactions.

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Corresponding author. E-mail address: jessehay{at}umich.edu.

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Molecular Biology of the Cell
Vol. 14, 698-720, February 2003
Copyright © 2003 by The American Society for Cell Biology

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