A splice variant of RILP induces lysosomal clustering independent of dynein recruitment.
The small GTPase Rab7 controls fusion and transport of late endocytic compartments. A critical mediator is the Rab7 effector RILP that recruits the minus-end dynein-dynactin motor complex to these compartments. We identified a natural occurring splice variant of RILP (RILPsv) lacking only 27 amino acids encoded by exon VII. Both variants bind Rab7, prolong its GTP-bound state, and induce clustering of late endocytic compartments. However, RILPsv does not recruit the dynein-dynactin complex, implicating exon VII in motor recruitment. Clustering might still occur via dimerization, since both RILP and RILPsv are able to form hetero- and homo-dimers. Moreover, both effectors compete for Rab7 binding but with different outcome for dynein-dynactin recruitment and transport. Hence, RILPsv provides an extra dimension to the control of vesicle fusion and transport by the small GTPase Rab7.
Marsman
Marije
M
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
Jordens
Ingrid
I
Rocha
Nuno
N
Kuijl
Coenraad
C
Janssen
Lennert
L
Neefjes
Jacques
J
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004398:Dyneins / Q000378:metabolism*; D004705:Endocytosis; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure*; D008545:Melanoma / Q000378:metabolism* / Q000648:ultrastructure; D020409:Molecular Motor Proteins / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D019154:Protein Splicing / Q000235:genetics; D013329:Structure-Activity Relationship; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier 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