Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites. Oppositely oriented microtubules form the basis for selective cargo trafficking in neurons, however the mechanisms that establish and maintain this organization are unclear. Here, we show that APC2, the brain-specific homolog of tumor-suppressor protein adenomatous polyposis coli (APC), promotes dynamics of minus-end-out microtubules in dendrites. We found that APC2 localizes as distinct clusters along microtubule bundles in dendrites and that this localization is driven by LC8-binding and two separate microtubule-interacting domains. Depletion of APC2 reduces the plus end dynamics of minus-end-out oriented microtubules, increases microtubule sliding, and causes defects in dendritic morphology. We propose a model in which APC2 regulates dendrite development by promoting dynamics of minus-end-out microtubules.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050278 | PMC |
| http://dx.doi.org/10.1038/s41467-018-05124-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unrestrained growth of correctly oriented microtubules instructs axonal microtubule orientation.
Elife
October 2022
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
In many eukaryotic cells, directed molecular transport occurs along microtubules. Within neuronal axons, transport over vast distances particularly relies on uniformly oriented microtubules, whose plus-ends point towards the distal axon tip (anterogradely polymerizing, or plus-end-out). However, axonal microtubules initially have mixed orientations, and how they orient during development is not yet fully understood.
View Article and Find Full Text PDFEndosomal Wnt signaling proteins control microtubule nucleation in dendrites.
PLoS Biol
March 2020
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Dendrite microtubules are polarized with minus-end-out orientation in Drosophila neurons. Nucleation sites concentrate at dendrite branch points, but how they localize is not known. Using Drosophila, we found that canonical Wnt signaling proteins regulate localization of the core nucleation protein γTubulin (γTub).
View Article and Find Full Text PDFMicrotubule Dynamics, Kinesin-1 Sliding, and Dynein Action Drive Growth of Cell Processes.
Biophys J
October 2018
Courant Institute of Mathematical Sciences and Department of Biology, New York University, New York City, New York. Electronic address:
Recent experimental studies of the role of microtubule sliding in neurite outgrowth suggested a qualitative model, according to which kinesin-1 motors push the minus-end-out microtubules against the cell membrane and generate the early cell processes. At the later stage, dynein takes over the sliding, expels the minus-end-out microtubules from the neurites, and pulls in the plus-end-out microtubules that continue to elongate the nascent axon. This model leaves unanswered a number of questions: why is dynein unable to generate the processes alone, whereas kinesin-1 can? What is the role of microtubule dynamics in process initiation and growth? Can the model correctly predict the rates of process growth in control and dynein-inhibited cases? What triggers the transition from kinesin-driven to dynein-driven sliding? To answer these questions, we combine computational modeling of a network of elastic dynamic microtubules and kinesin-1 and dynein motors with measurements of the process growth kinetics and pharmacological perturbations in Drosophila S2 cells.
View Article and Find Full Text PDFAPC2 controls dendrite development by promoting microtubule dynamics.
Nat Commun
July 2018
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
Mixed polarity microtubule organization is the signature characteristic of vertebrate dendrites. Oppositely oriented microtubules form the basis for selective cargo trafficking in neurons, however the mechanisms that establish and maintain this organization are unclear. Here, we show that APC2, the brain-specific homolog of tumor-suppressor protein adenomatous polyposis coli (APC), promotes dynamics of minus-end-out microtubules in dendrites.
View Article and Find Full Text PDFDifferentiation between Oppositely Oriented Microtubules Controls Polarized Neuronal Transport.
Neuron
December 2017
Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands. Electronic address:
Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!