TY - JOUR
T1 - Dynamic Palmitoylation Targets MAP6 to the Axon to Promote Microtubule Stabilization during Neuronal Polarization
AU - Tortosa, Elena
AU - Adolfs, Youri
AU - Fukata, Masaki
AU - Pasterkamp, R. Jeroen
AU - Kapitein, Lukas C
AU - Hoogenraad, Casper C.
N1 - Funding Information:
We thank Prof. Dr. Dieter Edbauer and Dr. Annie Andrieux for sharing MAP6 constructs and antibodies. We thank Dr. Norihiko Yokoi for performing initial palmitoylation experiments and Dr. Amélie Fréal and Dr. Gabriela Plucińska for their in-depth discussion. This work was supported by the Netherlands Organization for Scientific Research (NWO-ALW-VICI, C.C.H. and R.J.P.), the Foundation for Fundamental Research on Matter ([FOM] C.C.H.), which is part of the NWO, the Netherlands Organization for Health Research and Development (ZonMW-TOP, C.C.H.), the European Research Council (ERC) (ERC-consolidator, C.C.H.). E.T. received support by the Spanish Education Ministry and an FP7 European Union Marie Curie postdoctoral fellowship.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/5/17
Y1 - 2017/5/17
N2 - Microtubule-associated proteins (MAPs) are main candidates to stabilize neuronal microtubules, playing an important role in establishing axon-dendrite polarity. However, how MAPs are selectively targeted to specific neuronal compartments remains poorly understood. Here, we show specific localization of microtubule-associated protein 6 (MAP6)/stable tubule-only polypeptide (STOP) throughout neuronal maturation and its role in axonal development. In unpolarized neurons, MAP6 is present at the Golgi complex and in secretory vesicles. As neurons mature, MAP6 is translocated to the proximal axon, where it binds and stabilizes microtubules. Further, we demonstrate that dynamic palmitoylation, mediated by the family of α/β Hydrolase domain-containing protein 17 (ABHD17A-C) depalmitoylating enzymes, controls shuttling of MAP6 between membranes and microtubules and is required for MAP6 retention in axons. We propose a model in which MAP6's palmitoylation mediates microtubule stabilization, allows efficient organelle trafficking, and controls axon maturation in vitro and in situ.
AB - Microtubule-associated proteins (MAPs) are main candidates to stabilize neuronal microtubules, playing an important role in establishing axon-dendrite polarity. However, how MAPs are selectively targeted to specific neuronal compartments remains poorly understood. Here, we show specific localization of microtubule-associated protein 6 (MAP6)/stable tubule-only polypeptide (STOP) throughout neuronal maturation and its role in axonal development. In unpolarized neurons, MAP6 is present at the Golgi complex and in secretory vesicles. As neurons mature, MAP6 is translocated to the proximal axon, where it binds and stabilizes microtubules. Further, we demonstrate that dynamic palmitoylation, mediated by the family of α/β Hydrolase domain-containing protein 17 (ABHD17A-C) depalmitoylating enzymes, controls shuttling of MAP6 between membranes and microtubules and is required for MAP6 retention in axons. We propose a model in which MAP6's palmitoylation mediates microtubule stabilization, allows efficient organelle trafficking, and controls axon maturation in vitro and in situ.
KW - cytoskeleton
KW - MAP6
KW - microtubule stabilization
KW - microtubule-associated proteins
KW - neuronal polarity
KW - palmitoylation
KW - STOP
KW - α/β Hydrolase domain-containing protein (ABHD)
UR - http://www.scopus.com/inward/record.url?scp=85020107321&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2017.04.042
DO - 10.1016/j.neuron.2017.04.042
M3 - Article
C2 - 28521134
AN - SCOPUS:85020107321
SN - 0896-6273
VL - 94
SP - 809-825.e7
JO - Neuron
JF - Neuron
IS - 4
ER -