Role of kinesin light chain‐2 of kinesin‐1 in the traffic of Na,K‐ATPase‐containing vesicles in alveolar epithelial cells

Abstract

Recruitment of the Na,K-ATPase to the plasma membrane of alveolar epithelial cells results in increased active Na(+) transport and fluid clearance in a process that requires an intact microtubule network. However, the microtubule motors involved in this process have not been identified. In the present report, we studied the role of kinesin-1, a plus-end microtubule molecular motor that has been implicated in the movement of organelles in the Na,K-ATPase traffic. We determined by confocal microscopy and biochemical assays that kinesin-1 and the Na,K-ATPase are present in the same membranous cellular compartment. Knockdown of kinesin-1 heavy chain (KHC) or the light chain-2 (KLC2), but not of the light chain-1 (KLC1), decreased the movement of Na,K-ATPase-containing vesicles when compared to sham siRNA-transfected cells (control group). Thus, a specific isoform of kinesin-1 is required for microtubule-dependent recruitment of Na,K-ATPase to the plasma membrane, which is of physiological significance.

Role of Ostm1 Cytosolic Complex with Kinesin 5B in Intracellular Dispersion and Trafficking

“…KIF5B, a member of the kinesin-1 family (35), was shown to move along the microtubule cytoskeleton and promote, through adaptors, anterograde trafficking of multiple cellular cargos and organelles such as mitochondria and lysosomes (30,(42)(43)(44). Based on intracellular colocalization, Ostm1 cargos linked to KIF5B traffic specifically to lysosomes, whereas cargos destined for mitochondria likely involve other adaptors.…”

Hypoxia Leads to Na,K-ATPase Downregulation via Ca2+ Release-Activated Ca2+ Channels and AMPK Activation

“…Isolated perfused rat lung model. shRNAs against STIM1 and a nontargeting negative control were generated using the mCherry version of the pG-SUPER vector (a gift from Shin Kojima, Northwestern University, Evanston, IL) (47). The targeting sequence (sense) was 5Ј-AGGGAGGGTACCGAGAAT-3Ј.…”

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

“…However, no direct link between kinesins and ER membranes has been identified so far. More recently kinesin light chain (KLC) 2 has been found to be selectively involved in Na + / K + -ATPase trafficking to the plasma membrane (Trejo et al, 2010), and KLC1 appears to mediate trafficking of the transmembrane protein calsyntenin (Vagnoni et al, 2011). In this case, binding between the light chain and calsyntenin is direct and the motif in KLC1 that is responsible for this has been mapped (Konecna et al, 2006).…”