TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization

Elife. 2019 Jan 29:8:e38949. doi: 10.7554/eLife.38949.

Abstract

Dendritic arbors are crucial for nervous system assembly, but the intracellular mechanisms that govern their assembly remain incompletely understood. Here, we show that the dendrites of PVD neurons in Caenorhabditis elegans are patterned by distinct pathways downstream of the DMA-1 leucine-rich transmembrane (LRR-TM) receptor. DMA-1/LRR-TM interacts through a PDZ ligand motif with the guanine nucleotide exchange factor TIAM-1/GEF in a complex with act-4/Actin to pattern higher order 4° dendrite branches by localizing F-actin to the distal ends of developing dendrites. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. A partially redundant pathway, dependent on HPO-30/Claudin, regulates formation of 2° and 3° branches, possibly by regulating membrane localization and trafficking of DMA-1/LRR-TM. Collectively, our experiments suggest that HPO-30/Claudin localizes the DMA-1/LRR-TM receptor on PVD dendrites, which in turn can control dendrite patterning by directly modulating F-actin dynamics through TIAM-1/GEF.

Keywords: C. elegans; GEF independent; PVD; actin; claudin; dendrites; developmental biology; guanine nucleotide exchange factor; neuroscience.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Actins / metabolism
  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Claudins / genetics
  • Claudins / metabolism
  • Gene Expression Regulation
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Nervous System / cytology
  • Nervous System / growth & development
  • Nervous System / metabolism
  • Neurogenesis / genetics
  • Neuronal Plasticity / genetics*
  • Neurons / cytology
  • Neurons / metabolism
  • PDZ Domains
  • Protein Binding
  • Protein Transport
  • Synaptic Transmission
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics*
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • Claudins
  • DMA-1 protein, C elegans
  • Membrane Proteins
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • TIAM-1 protein, C elegans
  • hpo-30 protein, C elegans
  • rac1 GTP-Binding Protein