Asymmetric tethering by exocyst in vitro requires a Rab GTPase, an R-SNARE and a Sac1-sensitive phosphoinositide lipid.

Tethering factors play a critical role in deciphering the correct combination of vesicle and target membrane, before SNARE complex formation and membrane fusion. The exocyst plays a central role in tethering post-Golgi vesicles to the plasma membrane, although the mechanism by which this occurs is poorly understood. We recently established an assay for measuring exocyst-mediated vesicle tethering in vitro and we have adapted this assay to examine the ability of exocyst to tether vesicles in an asymmetric manner.

Development and Assessment of a Sustainable PhD Internship Program Supporting Diverse Biomedical Career Outcomes.

A doctoral-level internship program was developed at the University of North Carolina at Chapel Hill with the intent to create customizable experiential learning opportunities for biomedical trainees to support career exploration, preparation, and transition into their post-graduate professional roles. We report the outcomes of this program over a five-year period. During that 5-year period, 123 internships took place at over 70 partner sites, representing at least 20 academic, for-profit, and non-profit career paths in the life sciences.

Allosteric regulation of exocyst: Discrete activation of tethering by two spatial signals.

The exocyst imparts spatial control during exocytic vesicle tethering through its interactions with proteins and lipids on the vesicle and the plasma membrane. One such interaction is with the vesicle tether Sro7, although the outcome of this interaction is poorly understood. Here, we describe how Sro7 binding to the Exo84 subunit results in activation of the exocyst complex which leads to an increase in avidity for the Rab GTPase Sec4 and an increase in exocyst-mediated vesicle tethering.

Endosomal trafficking in schizophrenia.

Schizophrenia is a severe and heritable neuropsychiatric disorder, which arises due to a combination of common genetic variation, rare loss of function variation, and copy number variation. Functional genomic evidence has been used to identify candidate genes affected by this variation, which revealed biological pathways that may be disrupted in schizophrenia. Understanding the contributions of these pathways are critical next steps in understanding schizophrenia pathogenesis.

Schizophrenia-Linked Protein tSNARE1 Regulates Endosomal Trafficking in Cortical Neurons.

, which encodes the protein tSNARE1, is a high-confidence gene candidate for schizophrenia risk, but nothing is known about its cellular or physiological function. We identified the major gene products of and their cytoplasmic localization and function in endosomal trafficking in cortical neurons. We validated three primary isoforms of expressed in human brain, all of which encode a syntaxin-like Qa SNARE domain.