TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays

Sam F B van Beuningen; Lena Will; Martin Harterink; Anaël Chazeau; Eljo Y van Battum; Cátia P Frias; Mariella A M Franker; Eugene A Katrukha; Riccardo Stucchi; Karin Vocking; Ana T Antunes; Lotte Slenders; Sofia Doulkeridou; Peter Sillevis Smitt; A F Maarten Altelaar; Jan A Post; Anna Akhmanova; R Jeroen Pasterkamp; Lukas C Kapitein; Esther de Graaff; Casper C Hoogenraad

doi:10.1016/j.neuron.2015.11.012

TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays

Sam F B van Beuningen, Lena Will, Martin Harterink, Anaël Chazeau, Eljo Y van Battum, Cátia P Frias, Mariella A M Franker, Eugene A Katrukha, Riccardo Stucchi, Karin Vocking, Ana T Antunes, Lotte Slenders, Sofia Doulkeridou, Peter Sillevis Smitt, A F Maarten Altelaar, Jan A Post, Anna Akhmanova, R Jeroen Pasterkamp, Lukas C Kapitein, Esther de Graaff^*Casper C Hoogenraad^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Axon formation, the initial step in establishing neuronal polarity, critically depends on local microtubule reorganization and is characterized by the formation of parallel microtubule bundles. How uniform microtubule polarity is achieved during axonal development remains an outstanding question. Here, we show that the tripartite motif containing (TRIM) protein TRIM46 plays an instructive role in the initial polarization of neuronal cells. TRIM46 is specifically localized to the newly specified axon and, at later stages, partly overlaps with the axon initial segment (AIS). TRIM46 specifically forms closely spaced parallel microtubule bundles oriented with their plus-end out. Without TRIM46, all neurites have a dendrite-like mixed microtubule organization resulting in Tau missorting and altered cargo trafficking. By forming uniform microtubule bundles in the axon, TRIM46 is required for neuronal polarity and axon specification in vitro and in vivo. Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development.

Original language	English
Pages (from-to)	1208-1226
Journal	Neuron
Volume	88
Issue number	6
DOIs	https://doi.org/10.1016/j.neuron.2015.11.012
Publication status	Published - 16 Dec 2015

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10.1016/j.neuron.2015.11.012

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van Beuningen, S. F. B., Will, L., Harterink, M., Chazeau, A., van Battum, E. Y., Frias, C. P., Franker, M. A. M., Katrukha, E. A., Stucchi, R., Vocking, K., Antunes, A. T., Slenders, L., Doulkeridou, S., Sillevis Smitt, P., Altelaar, A. F. M., Post, J. A., Akhmanova, A., Pasterkamp, R. J., Kapitein, L. C., ... Hoogenraad, C. C. (2015). TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays. Neuron, 88(6), 1208-1226. https://doi.org/10.1016/j.neuron.2015.11.012

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title = "TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays",

abstract = "Axon formation, the initial step in establishing neuronal polarity, critically depends on local microtubule reorganization and is characterized by the formation of parallel microtubule bundles. How uniform microtubule polarity is achieved during axonal development remains an outstanding question. Here, we show that the tripartite motif containing (TRIM) protein TRIM46 plays an instructive role in the initial polarization of neuronal cells. TRIM46 is specifically localized to the newly specified axon and, at later stages, partly overlaps with the axon initial segment (AIS). TRIM46 specifically forms closely spaced parallel microtubule bundles oriented with their plus-end out. Without TRIM46, all neurites have a dendrite-like mixed microtubule organization resulting in Tau missorting and altered cargo trafficking. By forming uniform microtubule bundles in the axon, TRIM46 is required for neuronal polarity and axon specification in vitro and in vivo. Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development.",

author = "{van Beuningen}, {Sam F B} and Lena Will and Martin Harterink and Ana{\"e}l Chazeau and {van Battum}, {Eljo Y} and Frias, {C{\'a}tia P} and Franker, {Mariella A M} and Katrukha, {Eugene A} and Riccardo Stucchi and Karin Vocking and Antunes, {Ana T} and Lotte Slenders and Sofia Doulkeridou and {Sillevis Smitt}, Peter and Altelaar, {A F Maarten} and Post, {Jan A} and Anna Akhmanova and Pasterkamp, {R Jeroen} and Kapitein, {Lukas C} and {de Graaff}, Esther and Hoogenraad, {Casper C}",

year = "2015",

month = dec,

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doi = "10.1016/j.neuron.2015.11.012",

language = "English",

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van Beuningen, SFB , Will, L , Harterink, M, Chazeau, A, van Battum, EY, Frias, CP, Franker, MAM, Katrukha, EA, Stucchi, R, Vocking, K, Antunes, AT, Slenders, L, Doulkeridou, S, Sillevis Smitt, P, Altelaar, AFM , Post, JA , Akhmanova, A, Pasterkamp, RJ, Kapitein, LC , de Graaff, E & Hoogenraad, CC 2015, 'TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays', Neuron, vol. 88, no. 6, pp. 1208-1226. https://doi.org/10.1016/j.neuron.2015.11.012

TY - JOUR

T1 - TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays

AU - van Beuningen, Sam F B

AU - Will, Lena

AU - Harterink, Martin

AU - Chazeau, Anaël

AU - van Battum, Eljo Y

AU - Frias, Cátia P

AU - Franker, Mariella A M

AU - Katrukha, Eugene A

AU - Stucchi, Riccardo

AU - Vocking, Karin

AU - Antunes, Ana T

AU - Slenders, Lotte

AU - Doulkeridou, Sofia

AU - Sillevis Smitt, Peter

AU - Altelaar, A F Maarten

AU - Post, Jan A

AU - Akhmanova, Anna

AU - Pasterkamp, R Jeroen

AU - Kapitein, Lukas C

AU - de Graaff, Esther

AU - Hoogenraad, Casper C

PY - 2015/12/16

Y1 - 2015/12/16

N2 - Axon formation, the initial step in establishing neuronal polarity, critically depends on local microtubule reorganization and is characterized by the formation of parallel microtubule bundles. How uniform microtubule polarity is achieved during axonal development remains an outstanding question. Here, we show that the tripartite motif containing (TRIM) protein TRIM46 plays an instructive role in the initial polarization of neuronal cells. TRIM46 is specifically localized to the newly specified axon and, at later stages, partly overlaps with the axon initial segment (AIS). TRIM46 specifically forms closely spaced parallel microtubule bundles oriented with their plus-end out. Without TRIM46, all neurites have a dendrite-like mixed microtubule organization resulting in Tau missorting and altered cargo trafficking. By forming uniform microtubule bundles in the axon, TRIM46 is required for neuronal polarity and axon specification in vitro and in vivo. Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development.

AB - Axon formation, the initial step in establishing neuronal polarity, critically depends on local microtubule reorganization and is characterized by the formation of parallel microtubule bundles. How uniform microtubule polarity is achieved during axonal development remains an outstanding question. Here, we show that the tripartite motif containing (TRIM) protein TRIM46 plays an instructive role in the initial polarization of neuronal cells. TRIM46 is specifically localized to the newly specified axon and, at later stages, partly overlaps with the axon initial segment (AIS). TRIM46 specifically forms closely spaced parallel microtubule bundles oriented with their plus-end out. Without TRIM46, all neurites have a dendrite-like mixed microtubule organization resulting in Tau missorting and altered cargo trafficking. By forming uniform microtubule bundles in the axon, TRIM46 is required for neuronal polarity and axon specification in vitro and in vivo. Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development.

U2 - 10.1016/j.neuron.2015.11.012

DO - 10.1016/j.neuron.2015.11.012

M3 - Article

C2 - 26671463

SN - 0896-6273

VL - 88

SP - 1208

EP - 1226

JO - Neuron

JF - Neuron

IS - 6

ER -

TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays

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