PTRN-1, a microtubule minus end-binding CAMSAP homolog, promotes microtubule function in Caenorhabditis elegans neurons

Abstract

In neuronal processes, microtubules (MTs) provide structural support and serve as tracks for molecular motors. While it is known that neuronal MTs are more stable than MTs in non-neuronal cells, the molecular mechanisms underlying this stability are not fully understood. In this study, we used live fluorescence microscopy to show that the C. elegans CAMSAP protein PTRN-1 localizes to puncta along neuronal processes, stabilizes MT foci, and promotes MT polymerization in neurites. Electron microscopy revealed that ptrn-1 null mutants have fewer MTs and abnormal MT organization in the PLM neuron. Animals grown with a MT depolymerizing drug caused synthetic defects in neurite branching in the absence of ptrn-1 function, indicating that PTRN-1 promotes MT stability. Further, ptrn-1 null mutants exhibited aberrant neurite morphology and synaptic vesicle localization that is partially dependent on dlk-1. Our results suggest that PTRN-1 represents an important mechanism for promoting MT stability in neurons.

DOI: http://dx.doi.org/10.7554/eLife.01498.001

eLife digest

Microtubules are tiny tubular structures made from many copies of proteins called tubulins. Microtubules have a number of important roles inside cells: they are part of the cytoskeleton that provides structural support for the cell; they help to pull chromosomes apart during cell division; and they guide the trafficking of proteins and molecules around inside the cell. Most microtubules are relatively unstable, undergoing continuous dis-assembly and re-assembly in response to the needs of the cell. The microtubules in the branches of nerve cells are an exception, remaining relatively stable over time. Now Richardson et al. and, independently, Marcette et al., have shown that a protein called PTRN-1 has an important role in stabilizing the microtubules in the nerve cells of nematode worms.

By tagging the PTRN-1 proteins with fluorescent molecules, Richardson et al. were able to show that these proteins were present along the length of the microtubules within the nerve cells. Further work showed that the PTRN-1 proteins stabilize the microtubule filaments within the branches of these nerve cells and also hold them in position.

Richardson et al. also found that worms that had been genetically modified to prevent them from producing PTRN-1 failed to traffic certain molecules to the synapses between nerve cells. Moreover, these mutants also had problems with the branching of their nerve cells; however, these defects were relatively mild, which suggests that other molecules and proteins act in parallel with PTRN-1 to stabilize microtubules in nerve cells. Further work should be able to identify these factors and elucidate how they work together to stabilize the microtubules in nerve cells.

DOI: http://dx.doi.org/10.7554/eLife.01498.002