title: The microtubule minus-end-binding protein patronin/PTRN-1 is required for axon regeneration in C. elegans.
abstract: Precise regulation of microtubule (MT) dynamics is increasingly recognized as a critical determinant of axon regeneration. In contrast to developing neurons, mature axons exhibit noncentrosomal microtubule nucleation. The factors regulating noncentrosomal MT architecture in axon regeneration remain poorly understood. We report that PTRN-1, the C. elegans member of the Patronin/Nezha/calmodulin- and spectrin-associated protein (CAMSAP) family of microtubule minus-end-binding proteins, is critical for efficient axon regeneration in vivo. ptrn-1-null mutants display generally normal developmental axon outgrowth but significantly impaired regenerative regrowth after laser axotomy. Unexpectedly, mature axons in ptrn-1 mutants display elevated numbers of dynamic axonal MTs before and after injury, suggesting that PTRN-1 inhibits MT dynamics. The CKK domain of PTRN-1 is necessary and sufficient for its functions in axon regeneration and MT dynamics and appears to stabilize MTs independent of minus-end localization. Whereas in developing neurons, PTRN-1 inhibits activity of the DLK-1 mitogen-activated protein kinase (MAPK) cascade, we find that, in regeneration, PTRN-1 and DLK-1 function together to promote axonal regrowth.
authors.affiliation: Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Chuang
authors.affiliation: Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Goncharov
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Shaohe
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
authors.affiliation: Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: chisholm@ucsd.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D058105:Polymerization; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012038:Regeneration; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D013329:Structure-Activity Relationship; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; C000599463:PTRN-1 protein, C elegans