Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC class II molecules exert their function at the cell surface by presenting to T cells antigenic fragments that are generated in the endosomal pathway. The class II molecules are targetted to early lysosomal structures, termed MIIC, where they interact with antigenic fragments and are subsequently transported to the cell surface. We previously visualised vesicular transport of MHC class II-containing early lysosomes from the microtubule organising centre (MTOC) region towards the cell surface in living cells. Here we show that the MIIC move bidirectionally in a 'stop-and-go' fashion. Overexpression of a motor head-deleted kinesin inhibited MIIC motility, showing that kinesin is the motor that drives its plus end transport towards the cell periphery. Cytoplasmic dynein mediates the return of vesicles to the MTOC area and effectively retains the vesicles at this location, as assessed by inactivation of dynein by overexpression of dynamitin. Our data suggest a retention mechanism that determines the perinuclear accumulation of MIIC, which is the result of dynein activity being superior over kinesin activity. The bidirectional nature of MIIC movement is the result of both kinesin and dynein acting reciprocally on the MIIC during its transport. The motors may be the ultimate targets of regulatory kinases since the protein kinase inhibitor staurosporine induces a massive release of lysosomal vesicles from the MTOC region that is morphologically similar to that observed after inactivation of the dynein motor.
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PMID:Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments. 1003 29

Many intracellular compartments, including MHC class II-containing lysosomes, melanosomes, and phagosomes, move along microtubules in a bidirectional manner and in a stop-and-go fashion due to the alternating activities of a plus-end directed kinesin motor and a minus-end directed dynein-dynactin motor. It is largely unclear how motor proteins are targeted specifically to different compartments. Rab GTPases recruit and/or activate several proteins involved in membrane fusion and vesicular transport. They associate with specific compartments after activation, which makes Rab GTPases ideal candidates for controlling motor protein binding to specific membranes. We and others [7] have identified a protein, called RILP (for Rab7-interacting lysosomal protein), that interacts with active Rab7 on late endosomes and lysosomes. Here we show that RILP prevents further cycling of Rab7. RILP expression induces the recruitment of functional dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes. Consequently, these compartments are transported by these motors toward the minus end of microtubules, effectively inhibiting their transport toward the cell periphery. This signaling cascade may be responsible for timed and selective dynein motor recruitment onto late endosomes and lysosomes.
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PMID:The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. 1169 25