Neuronal depolarization modifies motor protein mobility.

TY - JOUR

T1 - Neuronal depolarization modifies motor protein mobility.

AU - Lardong, Kerstin

AU - Maas, Christoph

AU - Kneussel, Matthias

PY - 2009

Y1 - 2009

N2 - Active neuronal transport along microtubules participates in the targeting of mRNAs, proteins and organelles to their sites of action. Cytoplasmic dynein represents a minus-end-directed microtubule-dependent motor protein. Due to the polarity of microtubules in axonal and distal dendritic compartments, with microtubule minus-ends pointing toward the inside of the cell, dyneins mainly mediate retrograde transport pathways in neurons. Since dyneins transport synaptic proteins, we asked whether changes in neuronal activity would in general influence dynein transport. KCl-induced depolarization, a condition that mimics the effects of neuronal activity, or pharmacological blockade of neuronal action potentials, respectively, was combined with neuronal live cell imaging, using an autofluorescent dynein intermediate chain fusion (monomeric red fluorescent protein [mRFP]-dynein intermediate chain [DIC]) as a model protein. Notably, we found that induced activity significantly reduced dynein particle mobility, as well as both the total distance and velocity of movements in mouse cultured hippocampal neurons. In contrast, blockade of neuronal action potentials through TTX did not alter any of the parameters analyzed. Neuronal depolarization processes therefore represent candidate mechanisms to regulate intracellular transport of neuronal cargoes.

AB - Active neuronal transport along microtubules participates in the targeting of mRNAs, proteins and organelles to their sites of action. Cytoplasmic dynein represents a minus-end-directed microtubule-dependent motor protein. Due to the polarity of microtubules in axonal and distal dendritic compartments, with microtubule minus-ends pointing toward the inside of the cell, dyneins mainly mediate retrograde transport pathways in neurons. Since dyneins transport synaptic proteins, we asked whether changes in neuronal activity would in general influence dynein transport. KCl-induced depolarization, a condition that mimics the effects of neuronal activity, or pharmacological blockade of neuronal action potentials, respectively, was combined with neuronal live cell imaging, using an autofluorescent dynein intermediate chain fusion (monomeric red fluorescent protein [mRFP]-dynein intermediate chain [DIC]) as a model protein. Notably, we found that induced activity significantly reduced dynein particle mobility, as well as both the total distance and velocity of movements in mouse cultured hippocampal neurons. In contrast, blockade of neuronal action potentials through TTX did not alter any of the parameters analyzed. Neuronal depolarization processes therefore represent candidate mechanisms to regulate intracellular transport of neuronal cargoes.

M3 - SCORING: Zeitschriftenaufsatz

VL - 160

SP - 1

EP - 5

JO - NEUROSCIENCE

JF - NEUROSCIENCE

SN - 0306-4522

IS - 1

M1 - 1

ER -