Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development

Kah Wai Yau; Sam F B van Beuningen; Inês Cunha-Ferreira; Bas M C Cloin; Eljo Y van Battum; Lena Will; Philipp Schätzle; Roderick P Tas; Jaap van Krugten; Eugene A Katrukha; Kai Jiang; Phebe S Wulf; Marina Mikhaylova; Martin Harterink; R Jeroen Pasterkamp; Anna Akhmanova; Lukas C Kapitein; Casper C Hoogenraad

doi:10.1016/j.neuron.2014.04.019

Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development

Kah Wai Yau, Sam F B van Beuningen, Inês Cunha-Ferreira, Bas M C Cloin, Eljo Y van Battum, Lena Will, Philipp Schätzle, Roderick P Tas, Jaap van Krugten, Eugene A Katrukha, Kai Jiang, Phebe S Wulf, Marina Mikhaylova, Martin Harterink, R Jeroen Pasterkamp, Anna Akhmanova, Lukas C Kapitein, Casper C Hoogenraad

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

Abstract

In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.

Original language	English
Pages (from-to)	1058-73
Number of pages	16
Journal	Neuron
Volume	82
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2014.04.019
Publication status	Published - 4 Jun 2014

Keywords

Animals
Axons
Cytoskeletal Proteins
Dendrites
Hippocampus
Humans
Microtubules
Pyramidal Cells
Rats

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Yau, K. W., van Beuningen, S. F. B., Cunha-Ferreira, I., Cloin, B. M. C., van Battum, E. Y., Will, L., Schätzle, P., Tas, R. P., van Krugten, J., Katrukha, E. A., Jiang, K., Wulf, P. S., Mikhaylova, M., Harterink, M., Pasterkamp, R. J., Akhmanova, A., Kapitein, L. C., & Hoogenraad, C. C. (2014). Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development. Neuron, 82(5), 1058-73. https://doi.org/10.1016/j.neuron.2014.04.019

@article{f949bf9de6b242bdb0f15f90e0fe549a,

title = "Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development",

abstract = "In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.",

keywords = "Animals, Axons, Cytoskeletal Proteins, Dendrites, Hippocampus, Humans, Microtubules, Pyramidal Cells, Rats",

author = "Yau, {Kah Wai} and {van Beuningen}, {Sam F B} and In{\^e}s Cunha-Ferreira and Cloin, {Bas M C} and {van Battum}, {Eljo Y} and Lena Will and Philipp Sch{\"a}tzle and Tas, {Roderick P} and {van Krugten}, Jaap and Katrukha, {Eugene A} and Kai Jiang and Wulf, {Phebe S} and Marina Mikhaylova and Martin Harterink and Pasterkamp, {R Jeroen} and Anna Akhmanova and Kapitein, {Lukas C} and Hoogenraad, {Casper C}",

year = "2014",

month = jun,

day = "4",

doi = "10.1016/j.neuron.2014.04.019",

language = "English",

volume = "82",

pages = "1058--73",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

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}

Yau, KW, van Beuningen, SFB, Cunha-Ferreira, I, Cloin, BMC, van Battum, EY, Will, L, Schätzle, P, Tas, RP, van Krugten, J, Katrukha, EA, Jiang, K, Wulf, PS, Mikhaylova, M, Harterink, M, Pasterkamp, RJ, Akhmanova, A , Kapitein, LC & Hoogenraad, CC 2014, 'Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development', Neuron, vol. 82, no. 5, pp. 1058-73. https://doi.org/10.1016/j.neuron.2014.04.019

TY - JOUR

T1 - Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development

AU - Yau, Kah Wai

AU - van Beuningen, Sam F B

AU - Cunha-Ferreira, Inês

AU - Cloin, Bas M C

AU - van Battum, Eljo Y

AU - Will, Lena

AU - Schätzle, Philipp

AU - Tas, Roderick P

AU - van Krugten, Jaap

AU - Katrukha, Eugene A

AU - Jiang, Kai

AU - Wulf, Phebe S

AU - Mikhaylova, Marina

AU - Harterink, Martin

AU - Pasterkamp, R Jeroen

AU - Akhmanova, Anna

AU - Kapitein, Lukas C

AU - Hoogenraad, Casper C

PY - 2014/6/4

Y1 - 2014/6/4

N2 - In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.

AB - In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.

KW - Animals

KW - Axons

KW - Cytoskeletal Proteins

KW - Dendrites

KW - Hippocampus

KW - Humans

KW - Microtubules

KW - Pyramidal Cells

KW - Rats

U2 - 10.1016/j.neuron.2014.04.019

DO - 10.1016/j.neuron.2014.04.019

M3 - Article

C2 - 24908486

SN - 0896-6273

VL - 82

SP - 1058

EP - 1073

JO - Neuron

JF - Neuron

IS - 5

ER -

Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development

Abstract

Keywords

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