title: Heterotrimeric kinesin-2, together with kinesin-1, steers vesicular acetylcholinesterase movements toward the synapse.
abstract: Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression ofDrosophilaAChE tagged with photoactivatable green fluorescent protein andm-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity. GPAC-AChE, which is enriched in the neuropil region of the brain, moves in the apparently vesicular form in axons with an anterograde bias inDrosophilalarvae. Two anterograde motors, kinesin-1 and -2, propel distinct aspects of GPAC-AChE movements. Total loss of kinesin-2 reduces the density of anterograde traffic and increases bidirectional movements of GPAC-AChE vesicles without altering their speed. A partial loss of kinesin-1 reduces both the density and speed of anterograde GPAC-AChE traffic and enhances the pool of stationary vesicles. Together, these results suggest that combining activity of a relatively weak kinesin-2 with that of a stronger kinesin-1 motor could steer AChE-containing vesicles toward synapse, and provides a molecular basis for the observed subcellular distribution of the enzyme.-Kulkarni, A., Khan, Y., Ray, K. Heterotrimeric kinesin-2, together with kinesin-1, steers vesicular acetylcholinesterase movements toward the synapse.
authors.affiliation: Sophia College, Mumbai, India.|Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Anuttama
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Sophia College, Mumbai, India.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Khan
authors.affiliation: Tata Institute of Fundamental Research, Mumbai, India krishanu@tifr.res.in.
authors.forename: Krishanu
authors.initials: K
authors.lastname: Ray
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D021122:Protein Subunits; D000110:Acetylcholinesterase; D016547:Kinesins
keywords: Drosophila; intracellular transport; lateral-chordotonal-neuron; mouse brain