Lgr4 and Lgr5 drive the formation of long actin-rich cytoneme-like membrane protrusions.

Published

Journal Article

Embryonic development and adult tissue homeostasis require precise information exchange between cells and their microenvironment to coordinate cell behavior. A specialized class of ultra-long actin-rich filopodia, termed cytonemes, provides one mechanism for this spatiotemporal regulation of extracellular cues. We provide here a mechanism whereby the stem-cell marker Lgr5, and its family member Lgr4, promote the formation of cytonemes. Lgr4- and Lgr5-induced cytonemes exceed lengths of 80 µm, are generated through stabilization of nascent filopodia from an underlying lamellipodial-like network and functionally provide a pipeline for the transit of signaling effectors. As proof-of-principle, we demonstrate that Lgr5-induced cytonemes act as conduits for cell signaling by demonstrating that the actin motor and filopodial cargo carrier protein myosin X (Myo10) and the G-protein-coupled receptor (GPCR) signaling effector β-arrestin-2 (Arrb2) transit into cytonemes. This work delineates a biological function for Lgr4 and Lgr5 and provides the rationale to fully investigate Lgr4 and Lgr5 function and cytonemes in mammalian stem cell and cancer stem cell behavior.

Full Text

Duke Authors

Cited Authors

  • Snyder, JC; Rochelle, LK; Marion, S; Lyerly, HK; Barak, LS; Caron, MG

Published Date

  • March 15, 2015

Published In

Volume / Issue

  • 128 / 6

Start / End Page

  • 1230 - 1240

PubMed ID

  • 25653388

Pubmed Central ID

  • 25653388

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

Digital Object Identifier (DOI)

  • 10.1242/jcs.166322

Language

  • eng

Conference Location

  • England