KIF4 mediates anterograde translocation and positioning of ribosomal constituents to axons.
In this study, we have used a combination of biochemical and molecular biology techniques to demonstrate that the C-terminal tail domain of KIF4 directly interacts with P0, a major protein component of ribosomes. Besides, in dorsal root ganglion neurons, KIF4 and P0, as well as other ribosomal constituents, colocalize in clusters distributed along axons and neuritic tips. RNA interference suppression of KIF4 or expression of KIF4 variants lacking the tail domain or mutations of the ATP-binding site result in accumulation of P0 and other ribosomal proteins at the cell body and in their disappearance from axons. Our results also show one additional function for KIF4 involving an Ezrin-Radixin-Moesin-like domain in the second coiled-coiled region of KIF4. Expression of a KIF4 mutant lacking this domain abolishes the clustering of ribosomal constituents and prevents the anterograde translocation of the cell adhesion molecule L1. Taken together, the present results suggest that by binding to P0 through its tail domain and by using its motor activity, KIF4 is involved in the anterograde trafficking of ribosomal constituents to axons and that by means of its Ezrin-Radixin-Moesin-like domain interacts and transports L1.
Bisbal
Mariano
M
Laboratory of Neurobiology and Cell Biology, Instituto Investigación Médica Mercedes y Martín Ferreyra-Consejo Nacional de Investigaciones Científicas y Técnicas, 5016 Córdoba, Argentina.
Wojnacki
José
J
Peretti
Diego
D
Ropolo
Andrea
A
Sesma
Juliana
J
Jausoro
Ignacio
I
Cáceres
Alfredo
A
D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D051381:Rats; D012270:Ribosomes / Q000378:metabolism*
C089655:Kif4 protein, mouse; C540803:Kif4a protein, rat; D016547:Kinesins