A motor-driven mechanism for cell-length sensing

Cell Rep. 2012 Jun 28;1(6):608-16. doi: 10.1016/j.celrep.2012.05.013.

Abstract

Size homeostasis is fundamental in cell biology, but it is not clear how large cells such as neurons can assess their own size or length. We examined a role for molecular motors in intracellular length sensing.Computational simulations suggest that spatial information can be encoded by the frequency of an oscillating retrograde signal arising from a composite negative feedback loop between bidirectional motor-dependent signals. The model predicts that decreasing either or both anterograde or retrograde signals should increase cell length, and this prediction was confirmed upon application of siRNAs for specific kinesin and/or dynein heavy chains in adult sensory neurons. Heterozygous dynein heavy chain 1 mutant sensory neurons also exhibited increased lengths both in vitro and during embryonic development.Moreover, similar length increases were observed in mouse embryonic fibroblasts upon partial downregulation of dynein heavy chain 1.Thus, molecular motors critically influence cell length sensing and growth control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cell Size*
  • Computer Simulation
  • Cytoskeleton / metabolism
  • Down-Regulation
  • Dyneins / ultrastructure
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Flow Cytometry
  • Heterozygote
  • Kinesins / metabolism
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Biological
  • Molecular Motor Proteins / metabolism*
  • Mutation / genetics
  • NIH 3T3 Cells
  • Neurites / metabolism
  • RNA, Small Interfering / metabolism
  • Sciatic Nerve / cytology
  • Sciatic Nerve / ultrastructure
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism

Substances

  • Molecular Motor Proteins
  • RNA, Small Interfering
  • Dyneins
  • Kinesins