BDNF-mediated neurotransmission relies upon a myosin VI motor complex

Hiroko Yano; Ipe Ninan; Hong Zhang; Teresa A. Milner; Ottavio Arancio; Moses V. Chao

doi:10.1038/nn1730

BDNF-mediated neurotransmission relies upon a myosin VI motor complex

Hiroko Yano, Ipe Ninan, Hong Zhang, Teresa A. Milner, Ottavio Arancio, Moses V. Chao

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118 Scopus citations

Abstract

Brain-derived neurotrophic factor (BDNF) has been implicated in higher-order cognitive functions and in psychiatric disorders such as depression and schizophrenia. BDNF modulates synaptic transmission and plasticity primarily through the TrkB receptor, but the molecules involved in BDNF-mediated synaptic modulation are largely unknown. Myosin VI (Myo6) is a minus end-directed actin-based motor found in neurons that express Trk receptors. Here we report that Myo6 and a Myo6-binding protein, GIPC1, form a complex that can engage TrkB. Myo6 and GIPC1 were necessary for BDNF-TrkB-mediated facilitation of long-term potentiation in postnatal day 12-13 (P12-13) hippocampus. Moreover, BDNF-mediated enhancement of glutamate release from presynaptic terminals depended not only upon TrkB but also upon Myo6 and GIPC1. Similar defects in basal synaptic transmission as well as presynaptic properties were observed in Myo6 and GIPC1 mutant mice. Together, these results define an important role for the Myo6-GIPC1 motor complex in presynaptic function and in BDNF-TrkB-mediated synaptic plasticity.

Original language	English
Pages (from-to)	1009-1018
Number of pages	10
Journal	Nature neuroscience
Volume	9
Issue number	8
DOIs	https://doi.org/10.1038/nn1730
State	Published - Aug 2006

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@article{ba7b0965f1394b7983c3a3135b06cdb7,

title = "BDNF-mediated neurotransmission relies upon a myosin VI motor complex",

abstract = "Brain-derived neurotrophic factor (BDNF) has been implicated in higher-order cognitive functions and in psychiatric disorders such as depression and schizophrenia. BDNF modulates synaptic transmission and plasticity primarily through the TrkB receptor, but the molecules involved in BDNF-mediated synaptic modulation are largely unknown. Myosin VI (Myo6) is a minus end-directed actin-based motor found in neurons that express Trk receptors. Here we report that Myo6 and a Myo6-binding protein, GIPC1, form a complex that can engage TrkB. Myo6 and GIPC1 were necessary for BDNF-TrkB-mediated facilitation of long-term potentiation in postnatal day 12-13 (P12-13) hippocampus. Moreover, BDNF-mediated enhancement of glutamate release from presynaptic terminals depended not only upon TrkB but also upon Myo6 and GIPC1. Similar defects in basal synaptic transmission as well as presynaptic properties were observed in Myo6 and GIPC1 mutant mice. Together, these results define an important role for the Myo6-GIPC1 motor complex in presynaptic function and in BDNF-TrkB-mediated synaptic plasticity.",

author = "Hiroko Yano and Ipe Ninan and Hong Zhang and Milner, {Teresa A.} and Ottavio Arancio and Chao, {Moses V.}",

note = "Funding Information: We are grateful to N. Jenkins (National Cancer Institute, Frederick, Maryland) for porcine Myo6 cDNAs; T. Hasson (University of California, San Diego) for anti-Myo6 antibody; I. Taniuchi and D. Littman (New York University) for advice on the generation of Gipc1 mutant mice; A. Auerbach and staff members of the Transgenic Animal Facility (New York University) for assistance; R. Rajagopal, J.C. Arevalo, M. Beyna, D.B. Pereira and A.H. Kim for reagents and advice; D.C. Powell for writing the program for Matlab analysis; and I. Orozco and P.K. Hsu (Columbia University, New York) for assistance during electrophysiological experiments. This work was funded by US National Institutes of Health grants to M.V.C. (HD23315 and NS21072), O.A. (NS40045) and T.M. (HL-18974 and DA08259).",

year = "2006",

month = aug,

doi = "10.1038/nn1730",

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AU - Yano, Hiroko

AU - Ninan, Ipe

AU - Zhang, Hong

AU - Milner, Teresa A.

AU - Arancio, Ottavio

AU - Chao, Moses V.

N1 - Funding Information: We are grateful to N. Jenkins (National Cancer Institute, Frederick, Maryland) for porcine Myo6 cDNAs; T. Hasson (University of California, San Diego) for anti-Myo6 antibody; I. Taniuchi and D. Littman (New York University) for advice on the generation of Gipc1 mutant mice; A. Auerbach and staff members of the Transgenic Animal Facility (New York University) for assistance; R. Rajagopal, J.C. Arevalo, M. Beyna, D.B. Pereira and A.H. Kim for reagents and advice; D.C. Powell for writing the program for Matlab analysis; and I. Orozco and P.K. Hsu (Columbia University, New York) for assistance during electrophysiological experiments. This work was funded by US National Institutes of Health grants to M.V.C. (HD23315 and NS21072), O.A. (NS40045) and T.M. (HL-18974 and DA08259).

PY - 2006/8

Y1 - 2006/8

N2 - Brain-derived neurotrophic factor (BDNF) has been implicated in higher-order cognitive functions and in psychiatric disorders such as depression and schizophrenia. BDNF modulates synaptic transmission and plasticity primarily through the TrkB receptor, but the molecules involved in BDNF-mediated synaptic modulation are largely unknown. Myosin VI (Myo6) is a minus end-directed actin-based motor found in neurons that express Trk receptors. Here we report that Myo6 and a Myo6-binding protein, GIPC1, form a complex that can engage TrkB. Myo6 and GIPC1 were necessary for BDNF-TrkB-mediated facilitation of long-term potentiation in postnatal day 12-13 (P12-13) hippocampus. Moreover, BDNF-mediated enhancement of glutamate release from presynaptic terminals depended not only upon TrkB but also upon Myo6 and GIPC1. Similar defects in basal synaptic transmission as well as presynaptic properties were observed in Myo6 and GIPC1 mutant mice. Together, these results define an important role for the Myo6-GIPC1 motor complex in presynaptic function and in BDNF-TrkB-mediated synaptic plasticity.

AB - Brain-derived neurotrophic factor (BDNF) has been implicated in higher-order cognitive functions and in psychiatric disorders such as depression and schizophrenia. BDNF modulates synaptic transmission and plasticity primarily through the TrkB receptor, but the molecules involved in BDNF-mediated synaptic modulation are largely unknown. Myosin VI (Myo6) is a minus end-directed actin-based motor found in neurons that express Trk receptors. Here we report that Myo6 and a Myo6-binding protein, GIPC1, form a complex that can engage TrkB. Myo6 and GIPC1 were necessary for BDNF-TrkB-mediated facilitation of long-term potentiation in postnatal day 12-13 (P12-13) hippocampus. Moreover, BDNF-mediated enhancement of glutamate release from presynaptic terminals depended not only upon TrkB but also upon Myo6 and GIPC1. Similar defects in basal synaptic transmission as well as presynaptic properties were observed in Myo6 and GIPC1 mutant mice. Together, these results define an important role for the Myo6-GIPC1 motor complex in presynaptic function and in BDNF-TrkB-mediated synaptic plasticity.

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U2 - 10.1038/nn1730

DO - 10.1038/nn1730

M3 - Article

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VL - 9

SP - 1009

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JO - Nature neuroscience

JF - Nature neuroscience

IS - 8

ER -

BDNF-mediated neurotransmission relies upon a myosin VI motor complex

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