Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin

Yasuyuki Shima1, Mineko Kengaku, Tomoo Hirano

  • 1Department of Molecular Genetics, The Institute for Virus Research, Graduate School of Science, Kyoto University, Japan.

Developmental Cell
|August 7, 2004
PubMed

Insights

Mammalian Flamingo homolog Celsr2 is crucial for dendritic arborization in neurons. Loss of Celsr2 function leads to simplified dendritic structures, indicating its role in neuronal development and maintenance.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Drosophila Flamingo, a 7-pass transmembrane cadherin, is vital for dendritic patterning and axon guidance.
  • The molecular mechanisms and mammalian homolog roles of Flamingo remain largely unknown.

Purpose of the Study:

  • To investigate the function of the mammalian Flamingo homolog, Celsr2, in neuronal development.
  • To elucidate the molecular basis of Celsr2's role in dendritic patterning.

Main Methods:

  • Loss-of-function analysis utilizing RNA interference (RNAi).
  • Experiments conducted in organotypic brain slice cultures.
  • Analysis of dendritic morphology in cortical pyramidal neurons and Purkinje neurons.

Main Results:

  • Knockdown of Celsr2 caused significant simplification of dendritic arbors.
  • Phenotype observed was attributed to dendritic branch retraction.
  • Cadherin-mediated homophilic interaction is essential for dendritic branch maintenance.
  • Specific Celsr2 extracellular and intracellular regions influenced cellular responses.

Conclusions:

  • Celsr2 plays a critical role in maintaining dendritic arbor complexity in mammalian neurons.
  • Homophilic interactions mediated by Celsr2 are necessary for dendritic maintenance.
  • Distinct functional domains within Celsr2 regulate its role in dendritic growth and maintenance.

Related Concept Videos

Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...