WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility

J Cell Biol. 2017 Jun 5;216(6):1673-1688. doi: 10.1083/jcb.201701074. Epub 2017 May 4.


Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call "α-motility." Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE-activators of branched actin assembly-make actin-filled pseudopods. Although SCAR has been shown to drive pseudopod formation, WASP's role in this process is controversial. We hypothesize that these genes collectively represent a genetic signature of α-motility because both are used for pseudopod formation. WASP depletion from human neutrophils confirms that both proteins are involved in explosive actin polymerization, pseudopod formation, and cell migration. WASP and WAVE also colocalize to dynamic signaling structures. Moreover, retention of WASP together with SCAR correctly predicts α-motility in disease-causing chytrid fungi, which we show crawl at >30 µm/min with actin-filled pseudopods. By focusing on one migration mode in many eukaryotes, we identify a genetic marker of pseudopod formation, the morphological feature of α-motility, providing evidence for a widely distributed mode of cell crawling with a single evolutionary origin.

Publication types

  • Comparative Study
  • Video-Audio Media
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism*
  • Animals
  • Cell Movement*
  • Chemotaxis
  • Chytridiomycota / genetics
  • Chytridiomycota / metabolism*
  • Computational Biology
  • Data Mining
  • Databases, Genetic
  • Evolution, Molecular*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Genomics / methods
  • HL-60 Cells
  • Humans
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Neutrophils / metabolism*
  • Phylogeny
  • Pseudopodia / metabolism*
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection
  • Wiskott-Aldrich Syndrome Protein / genetics
  • Wiskott-Aldrich Syndrome Protein / metabolism*
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / metabolism*


  • Actin-Related Protein 2-3 Complex
  • Actins
  • Fungal Proteins
  • WAS protein, human
  • WASF1 protein, human
  • Wiskott-Aldrich Syndrome Protein
  • Wiskott-Aldrich Syndrome Protein Family

Associated data

  • GENBANK/BC012738
  • RefSeq/XP_004994362
  • RefSeq/XP_004997564