Cromberg, L.E.; Saez, T.M.M.; Otero, M.G.; Tomasella, E.; Alloatti, M.; Damianich, A.; Pozo Devoto, V.; Ferrario, J.; Gelman, D.; Rubinstein, M.; Falzone, T.L. "Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors" (2019) Journal of Neurochemistry
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The process of locomotion is controlled by fine-tuned dopaminergic neurons in the Substantia Nigra pars-compacta (SNpc) that projects their axons to the dorsal striatum regulating cortical innervations of medium spiny neurons. Dysfunction in dopaminergic neurotransmission within the striatum leads to movement impairments, gaiting defects, and hypo-locomotion. Due to their high polarity and extreme axonal arborization, neurons depend on molecular motor proteins and microtubule-based transport for their normal function. Transport defects have been associated with neurodegeneration since axonopathies, axonal clogging, microtubule destabilization, and lower motor proteins levels were described in the brain of patients with Parkinson's Disease and other neurodegenerative disorders. However, the contribution of specific motor proteins to the regulation of the nigrostriatal network remains unclear. Here, we generated different conditional knockout mice for the kinesin heavy chain 5B subunit (Kif5b) of Kinesin-1 to unravel its contribution to locomotion. Interestingly, mice with neuronal Kif5b deletion showed hypo-locomotion, movement initiation deficits, and coordination impairments. High pressure liquid chromatography determined that dopamine (DA) metabolism is impaired in neuronal Kif5b-KO, while no dopaminergic cell loss was observed. However, the deletion of Kif5b only in dopaminergic neurons is not sufficient to induce locomotor defects. Noteworthy, pharmacological stimulation of DA release together with agonist or antagonist of DA receptors revealed selective D2-dependent movement initiation defects in neuronal Kif5b-KO. Finally, subcellular fractionation from striatum showed that Kif5b deletion reduced the amount of dopamine D2 receptor in synaptic plasma membranes. Together, these results revealed an important role for Kif5b in the modulation of the striatal network that is relevant to the overall locomotor response. Open Science Badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at (Figure presented.). Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: © 2019 International Society for Neurochemistry


Documento: Artículo
Título:Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors
Autor:Cromberg, L.E.; Saez, T.M.M.; Otero, M.G.; Tomasella, E.; Alloatti, M.; Damianich, A.; Pozo Devoto, V.; Ferrario, J.; Gelman, D.; Rubinstein, M.; Falzone, T.L.
Filiación:Instituto de Biología Celular y Neurociencias IBCN (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Biología y Medicina Experimental IBYME (CONICET), Buenos Aires, Argentina
Instituto de Investigaciones Farmacológicas ININFA, (CONICET-UBA), Buenos Aires, Argentina
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular INGEBI (CONICET), Buenos Aires, Argentina
Center for Translational Medicine (CTM), International Clinical Research Center, St. Anne's University Hospital (ICRC-FNUSA), Brno, Czech Republic
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:axonal transport; dopamine; dopamine receptors; Kif5b; locomotor response; nigrostriatal pathway
Título revista:Journal of Neurochemistry
Título revista abreviado:J. Neurochem.


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---------- APA ----------
Cromberg, L.E., Saez, T.M.M., Otero, M.G., Tomasella, E., Alloatti, M., Damianich, A., Pozo Devoto, V.,..., Falzone, T.L. (2019) . Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors. Journal of Neurochemistry.
---------- CHICAGO ----------
Cromberg, L.E., Saez, T.M.M., Otero, M.G., Tomasella, E., Alloatti, M., Damianich, A., et al. "Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors" . Journal of Neurochemistry (2019).
---------- MLA ----------
Cromberg, L.E., Saez, T.M.M., Otero, M.G., Tomasella, E., Alloatti, M., Damianich, A., et al. "Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors" . Journal of Neurochemistry, 2019.
---------- VANCOUVER ----------
Cromberg, L.E., Saez, T.M.M., Otero, M.G., Tomasella, E., Alloatti, M., Damianich, A., et al. Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors. J. Neurochem. 2019.