Molecular dissection of the Munc18c/syntaxin4 interaction: Implications for regulation of membrane trafficking

Sec1p/Munc18 (SM) proteins are believed to play an integral role in vesicle transport through their interaction with SNAREs. Different SM proteins have been shown to interact with SNAREs via different mechanisms, leading to the conclusion that their function has diverged. To further explore this notion, in this study, we have examined the molecular interactions between Munc18c and its cognate SNAREs as these molecules are ubiquitously expressed in mammals and likely regulate a universal plasma membrane trafficking step. Thus, Munc18c binds to monomeric syntaxin4 and the N-terminal 29 amino acids of syntaxin4 are necessary for this interaction. We identified key residues in Munc18c and syntaxin4 that determine the N-terminal interaction and that are consistent with the N-terminal binding mode of yeast proteins Sly1p and Sed5p. In addition, Munc18c binds to the syntaxin4/SNAP23/VAMP2 SNARE complex. Pre-assembly of the syntaxin4/Munc18c dimer accelerates the formation of SNARE complex compared to assembly with syntaxin4 alone. These data suggest that Munc18c interacts with its cognate SNAREs in a manner that resembles the yeast proteins Sly1p and Sed5p rather than the mammalian neuronal proteins Munc18a and syntaxin1a. The Munc18c-SNARE interactions described here imply that Munc18c could play a positive regulatory role in SNARE assembly.

Goal orientation, ability and task performance: A moderated analysis

Achievement goal orientation represents an individual's general approach to an achievement situation, and has important implications for how individuals react to novel, challenging tasks. However, theorists such as Yeo and Neal (2004) have suggested that the effects of goal orientation may emerge over time. Bell and Kozlowski (2002) have further argued that these effects may be moderated by individual ability. The current study tested the dynamic effects of a new 2x2 model of goal orientation (mastery/performance x approach/avoidance) on performance on a simulated air traffic control (ATC) task, as moderated by dynamic spatial ability. One hundred and one first-year participants completed a self-report goal orientation measure and computerbased dynamic spatial ability test and performed 30 trials of an ATC task. Hypotheses were tested using a two-level hierarchical linear model. Mastery-approach orientation was positively related to task performance, although no interaction with ability was observed. Performance-avoidance orientation was negatively related to task performance; this association was weaker at high levels of ability. Theoretical and practical implications will be discussed.