Investigation of the Nup358 Recruitment of Kinesin-1 Light Chain 2 Reveals Importance of Residues Flanking LEWD Motif

Authors: Atara Fishman, Sozanne Solmaz

Field of Study: Biological Sciences; Mathematical Sciences

Program Affiliation: Solmaz Lab in Biochemistry and Structural Biology

Faculty Mentors: Sozanne Solmaz

Easel: 101

Timeslot: Midday

Abstract: Kinesin-1, a motor protein responsible for anterograde cargo transport toward the microtubule plus end, is a heterotetramer composed of two heavy chains (KHC) containing the motor domain, and two light chains (KLC) mediating cargo recognition and autoinhibition. For cargo recognition, short W-acidic motifs are recognized by KLC2. Specifically, a W-acidic LEWD motif on Nup358, a 358kDa nucleoporin subunit of the nuclear pore complex recruits Kinesin-1. This sequence on Nup358 is sufficient for the recruitment of KLC2, although the role of flanking residues remains poorly defined. These experiments investigate the importance of these residues, demonstrating that LEWD-flanking residues are likely also crucial for recruiting KLC2, as mutations at these sites significantly reduce the binding of KLC2 to Nup358. The interaction of KLC2 with Nup358 is crucial for activation of the Kinesin-1 motor and facilitates a nuclear positioning pathway essential for generation of the majority of neurons and glia cells in the brain.