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

Abstract

Dendritic arbors are a 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 4º 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 2º and 3º 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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Leo TH Tang

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Carlos A Diaz-Balzac

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4723-1282
  3. Maisha Rahman

    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nelson J Ramirez-Suarez

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7394-860X
  5. Yehuda Salzberg

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria I Lázaro-Peña

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hannes E Bülow

    Department of Genetics, Albert Einstein College of Medicine, New York, United States
    For correspondence
    hannes.buelow@einstein.yu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6271-0572

Funding

National Institute of Neurological Disorders and Stroke (R21NS081505)

  • Hannes E Bülow

National Institute of General Medical Sciences (T32GM007288)

  • Carlos A Diaz-Balzac

Eunice Kennedy Shriver National Institute of Child Health and Human Development (F31HD066967)

  • Carlos A Diaz-Balzac

Fulbright-Colciencias

  • Nelson J Ramirez-Suarez

Irma T Hirschl/Monique Weill-Caulier

  • Hannes E Bülow

National Institute of Neurological Disorders and Stroke (F31NS100370)

  • Maisha Rahman

National Institute of General Medical Sciences (T32GM07491)

  • Maria I Lázaro-Peña

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Shai Shaham, The Rockefeller University, United States

Version history

  1. Received: June 5, 2018
  2. Accepted: January 28, 2019
  3. Accepted Manuscript published: January 29, 2019 (version 1)
  4. Version of Record published: February 11, 2019 (version 2)

Copyright

© 2019, Tang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,033
    views
  • 239
    downloads
  • 25
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Leo TH Tang
  2. Carlos A Diaz-Balzac
  3. Maisha Rahman
  4. Nelson J Ramirez-Suarez
  5. Yehuda Salzberg
  6. Maria I Lázaro-Peña
  7. Hannes E Bülow
(2019)
TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization
eLife 8:e38949.
https://doi.org/10.7554/eLife.38949

Share this article

https://doi.org/10.7554/eLife.38949

Further reading

    1. Developmental Biology
    Edgar M Pera, Josefine Nilsson-De Moura ... Ivana Milas
    Research Article

    We previously showed that SerpinE2 and the serine protease HtrA1 modulate fibroblast growth factor (FGF) signaling in germ layer specification and head-to-tail development of Xenopus embryos. Here, we present an extracellular proteolytic mechanism involving this serpin-protease system in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte, and craniofacial cartilage formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection of Sdc4 mRNA partially rescued NC migration defects induced by both HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism:

    SerpinE2 ┤HtrA1 protease ┤Syndecan-4 → NC cell migration.

    1. Developmental Biology
    2. Neuroscience
    Kristine B Walhovd, Stine K Krogsrud ... Didac Vidal-Pineiro
    Research Article

    Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4–82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.