Molecular Neurobiology

, Volume 54, Issue 8, pp 6085–6096 | Cite as

The Motor KIF5C Links the Requirements of Stable Microtubules and IGF-1 Receptor Membrane Insertion for Neuronal Polarization

  • Mariana Oksdath
  • Alvaro F. Nieto Guil
  • Diego Grassi
  • Lucas J. Sosa
  • Santiago Quiroga


Three early signals of asymmetry have been described to occur in a single neurite of neurons at stage 2 of differentiation (before polarization) and shown to be essential for neuronal polarization: (i) accumulation of stable microtubules, (ii) enrichment of the plasma membrane with activatable IGF-1r, and (iii) polarized transport of the microtubular motor KIF5C. Here, we studied the possible relationship between these three phenomena. Our results show that the activatable (membrane-inserted) IGF-1r and stable microtubules accumulate in the same neurite of cells at stage 2. The polarized insertion of IGF-1r depends on microtubule dynamics as shown using drugs which modify microtubule stability. Silencing of KIF5C expression prevents the polarized insertion of IGF-1r into the neuronal plasmalemma and neuronal polarization. Syntaxin 6 and VAMP4, necessary for the polarized insertion of the IGF-1r, are associated to vesicles carried by the microtubular motor KIF5C and is transported preferentially to the neurite where KIF5C accumulates. We conclude that the enrichment of stable microtubules in the future axon enhances KIF5C-mediated vesicular transport of syntaxin 6 and VAMP4, which in turn mediates the polarized insertion of IGF-1r in the plasmalemma, a key step for neuronal polarization. We herewith establish a mechanistic link between three early polarity events necessary for the establishment of neuronal polarity.


Neuronal differentiation Neuronal polarization IGF-1 receptor KIF5C Stable microtubules Syntaxin 6 



This work was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica, Argentina, PICT 1554 and 1646 (to SQ) and by the Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba (SECYT-UNC-to SQ). We are indebted to Dr. Jennifer Petersen and Dr. Daniel Choquet for their help with the spinning disk microscopy experiments and to Dr. Corinne Lasmezas for critical reading of the manuscript.

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

Supplementary material

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High resolution image (TIFF 1969 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias QuímicasUniversidad Nacional de Córdoba-CONICETCórdobaArgentina

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