Pivotal role of translokin/CEP57 in the unconventional secretion versus nuclear translocation of FGF2.
Intracellular trafficking of fibroblast growth factor 2 (FGF2) exhibits two unusual features: (i) it is secreted despite the lack of signal peptide and (ii) it can translocate to the nucleus after interaction with high- and low-affinity receptors on the cell surface, although it does not possess any classical nuclear localization signal. This nuclear translocation constitutes an important part of the response to the growth factor. Previously, we identified Translokin/CEP57, an FGF2 binding partner, as an intracellular mediator of FGF2 trafficking, which is essential for the nuclear translocation of the growth factor. Here, we report the identification of four Translokin partners: sorting nexin 6, Ran-binding protein M and the kinesins KIF3A and KIF3B. These proteins, through their interaction with Translokin, are involved in two exclusive complexes allowing the bidirectional trafficking of FGF2. Thus, Translokin plays a pivotal role in this original mechanism. In addition, we show that FGF2 secretion is regulated by a negative loop, retro-controlled by FGF receptor and involving FGF2 itself.
INSERM U858, F-31432 Toulouse, France.
Sylvain
S
Meunier
Marina García-Jove
MG
Navarro
Carine
C
Bossard
Henrik
H
Laurell
Christian
C
Touriol
Eric
E
Lacazette
Hervé
H
Prats
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D018076:DNA, Complementary; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D034741:RNA, Small Interfering; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D034741:RNA, Small Interfering; C482107:Tsp57 protein, mouse; D016222:Fibroblast Growth Factor 2