In Vivo Neuron‐Wide Analysis of Synaptic Vesicle Precursor Trafficking

• Published in: Traffic (Copenhagen, Denmark) Vol. 15; no. 3; pp. 273 - 291
• Main Authors: Maeder, Celine I., San‐Miguel, Adriana, Wu, Emily Ye, Lu, Hang, Shen, Kang
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.03.2014; Wiley Subscription Services, Inc
• Subjects: Animals; Axonal Transport; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; kinesin; mathematical model; Motor Neurons - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; synaptic vesicle precursor; Synaptic Vesicles - metabolism; transport; mathematical model; synaptic vesicle precursor; transport; kinesin
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/tra.12142

During synapse development, synaptic proteins must be targeted to sites of presynaptic release. Directed transport as well as local sequestration of synaptic vesicle precursors (SVPs), membranous organelles containing many synaptic proteins, might contribute to this process. Using neuron‐wide time‐lapse microscopy, we studied SVP dynamics in the DA9 motor neuron in Caenorhabditis elegans. SVP transport was highly dynamic and bi‐directional throughout the entire neuron, including the dendrite. While SVP trafficking was anterogradely biased in axonal segments prior to the synaptic domain, directionality of SVP movement was stochastic in the dendrite and distal axon. Furthermore, frequency of movement and speed were variable between different compartments. These data provide evidence that SVP transport is differentially regulated in distinct neuronal domains. It also suggests that polarized SVP transport in concert with local vesicle capturing is necessary for accurate presynapse formation and maintenance. SVP trafficking analysis of two hypomorphs for UNC‐104/KIF1A in combination with mathematical modeling identified directionality of movement, entry of SVPs into the axon as well as axonal speeds as the important determinants of steady‐state SVP distributions. Furthermore, detailed dissection of speed distributions for wild‐type and unc‐104/kif1a mutant animals revealed an unexpected role for UNC‐104/KIF1A in dendritic SVP trafficking. During synapse development, synaptic proteins must be targeted to presynaptic sites. Using neuron‐wide time‐lapse microscopy in Caenorhabditis elegans, we show that synaptic vesicle precursor (SVP) transport is differentially regulated in axon and dendrites and that polarized transport in concert with local vesicle capturing is necessary for accurate presynapse formation. SVP trafficking analysis of two hypomorphs for UNC‐104/KIF1A in combination with mathematical modeling identified movement directionality, entry of SVPs into the axon and axonal speeds as the important determinants of steady‐state SVP distributions.