The conserved kinase UNC-51 acts with VAB-8 and UNC-14 to regulate axon outgrowth in C. elegans

Tina Lai1, Gian Garriga

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Development (Cambridge, England)
|November 13, 2004
PubMed

Insights

Researchers discovered how VAB-8 and UNC-14 proteins interact with UNC-51 kinase to guide neuronal growth cones. This interaction is crucial for posterior axon guidance in C. elegans, revealing a new mechanism for anteroposterior neuronal development.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Directional cues are essential for neuronal growth cone migration.
  • While dorsoventral guidance mechanisms are understood (e.g., UNC-6/netrin), anteroposterior guidance remains less clear.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying anteroposterior axon guidance.
  • To investigate the role of VAB-8 and its interaction with UNC-51 in neuronal migration.

Main Methods:

  • Described a physical interaction between VAB-8 and UNC-51.
  • Utilized genetic analysis in C. elegans CAN neurons.
  • Assessed the impact of peptide interference on axon outgrowth.

Main Results:

  • VAB-8 and UNC-51 function in CAN neurons for posterior axon guidance.
  • Disruption of UNC-51 interactions with VAB-8 or UNC-14 impaired CAN axon outgrowth.
  • Provided genetic evidence for VAB-8 acting in an UNC-51 pathway.

Conclusions:

  • VAB-8 and UNC-14 are substrates mediating UNC-51 function in axon outgrowth.
  • This study reveals a novel mechanism for anteroposterior axon guidance.
  • The findings contribute to understanding conserved pathways in neuronal development.

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...