Kinesin-2 is a motor for late endosomes and lysosomes.
The bidirectional nature of late endosome/lysosome movement suggests involvement of at least two distinct motors, one minus-end directed and one plus-end directed. Previous work has identified dynein as the minus-end-directed motor for late endosome/lysosome localization and dynamics. Conventional kinesin (kinesin-1) has been implicated in plus-end-directed late endosome/lysosome movement, but other kinesin family members may also be involved. Kinesin-2 is known to drive the movement of pigment granules, a type of lysosomally derived organelle, and was recently found to be associated with purified late endosomes. To determine whether kinesin-2 might also power endosome movement in non-pigmented cells, we overexpressed dominant negative forms of the KIF3A motor subunit and KAP3 accessory subunit and knocked down KAP3 levels using RNAi. We found kinesin-2 to be required for the normal steady-state localization of late endosomes/lysosomes but not early endosomes or recycling endosomes. Despite the abnormal subcellular distribution of late endosomes/lysosomes, the uptake and trafficking of molecules through the conventional endocytic pathway appeared to be unaffected. The slow time-course of inhibition suggests that both kinesin-2 itself and its attachment to membranes do not turn over quickly.
Brown
Christa L
CL
Department of Biology, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Maier
Kerstin C
KC
Stauber
Tobias
T
Ginkel
Laura M
LM
Wordeman
Linda
L
Vernos
Isabelle
I
Schroer
Trina A
TA
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins; D008247:Lysosomes / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
D008869:Microtubule-Associated Proteins; D016547:Kinesins