TY - JOUR
T1 - Rab35 and its effectors promote formation of tunneling nanotubes in neuronal cells
AU - Bhat, Shaarvari
AU - Ljubojevic, Nina
AU - Zhu, Seng
AU - Fukuda, Mitsunori
AU - Echard, Arnaud
AU - Zurzolo, Chiara
N1 - Funding Information:
The authors thank Christopher Westlake for providing the EHD1 construct. We are very grateful to Stéphanie Lebreton for critical discussions related to the project and to Michael Henderson for editing the manuscript. We acknowledge the Center for Translational Science (CRT)-Cytometry and Biomarkers Unit of Technology and Service (CB UTechS) and Imagopole-Citech of Institut Pasteur for support in conducting this study. Finally, we thank all C.Z. lab members for discussions on the project. We are also grateful for the financial support of Institut Pasteur (Paris). S.B. is supported by JPND-NeuTARGETs-ANR-14-JPCD-0002-02 and INSERM (HTE201602). N.L. is supported by Sorbonne Université—doctoral grant number 3210/2018. S.Z. was supported by Ph.D. fellowships from the China Scholarship Council (201306170046) and by an Institute Carnot fellowship.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Tunneling nanotubes (TNTs) are F-actin rich structures that connect distant cells, allowing the transport of many cellular components, including vesicles, organelles and molecules. Rab GTPases are the major regulators of vesicle trafficking and also participate in actin cytoskeleton remodelling, therefore, we examined their role in TNTs. Rab35 functions with several proteins that are involved in vesicle trafficking such as ACAP2, MICAL-L1, ARF6 and EHD1, which are known to be involved in neurite outgrowth. Here we show that Rab35 promotes TNT formation and TNT-mediated vesicle transfer in a neuronal cell line. Furthermore, our data indicates that Rab35-GTP, ACAP2, ARF6-GDP and EHD1 act in a cascade mechanism to promote TNT formation. Interestingly, MICAL-L1 overexpression, shown to be necessary for the action of Rab35 on neurite outgrowth, showed no effect on TNTs, indicating that TNT formation and neurite outgrowth may be processed through similar but not identical pathways, further supporting the unique identity of these cellular protrusions.
AB - Tunneling nanotubes (TNTs) are F-actin rich structures that connect distant cells, allowing the transport of many cellular components, including vesicles, organelles and molecules. Rab GTPases are the major regulators of vesicle trafficking and also participate in actin cytoskeleton remodelling, therefore, we examined their role in TNTs. Rab35 functions with several proteins that are involved in vesicle trafficking such as ACAP2, MICAL-L1, ARF6 and EHD1, which are known to be involved in neurite outgrowth. Here we show that Rab35 promotes TNT formation and TNT-mediated vesicle transfer in a neuronal cell line. Furthermore, our data indicates that Rab35-GTP, ACAP2, ARF6-GDP and EHD1 act in a cascade mechanism to promote TNT formation. Interestingly, MICAL-L1 overexpression, shown to be necessary for the action of Rab35 on neurite outgrowth, showed no effect on TNTs, indicating that TNT formation and neurite outgrowth may be processed through similar but not identical pathways, further supporting the unique identity of these cellular protrusions.
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U2 - 10.1038/s41598-020-74013-z
DO - 10.1038/s41598-020-74013-z
M3 - Article
C2 - 33033331
AN - SCOPUS:85092316582
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 16803
ER -