The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors.
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.
Jordens
I
I
Division of Tumour Biology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
Fernandez-Borja
M
M
Marsman
M
M
Dusseljee
S
S
Janssen
L
L
Calafat
J
J
Janssen
H
H
Wubbolts
R
R
Neefjes
J
J
D048868:Adaptor Proteins, Signal Transducing; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; C423317:RILP protein, human; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D004398:Dyneins; D020691:rab GTP-Binding Proteins