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Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):E3845-54. doi: 10.1073/pnas.1509098112. Epub 2015 Jun 30.

Novel protein Callipygian defines the back of migrating cells.

Author information

1
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
2
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD 21218.
3
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; pnd@jhmi.edu.

Abstract

Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or "clustered," to the cell rear is immobile, but when polarity is disrupted, it disperses throughout the membrane and responds to uniform chemoattractant stimulation by transiently localizing to the cytosol. These behaviors require a pleckstrin homology-domain membrane tether and a WD40 clustering domain, which can also direct other membrane proteins to the back. Fragments of CynA lacking the pleckstrin homology domain, which are normally found in the cytosol, localize to the lagging edge membrane when coexpressed with full-length protein, showing that CynA clustering is mediated by oligomerization. Cells lacking CynA have aberrant lateral protrusions, altered leading-edge morphology, and decreased directional persistence, whereas those overexpressing the protein display exaggerated features of polarity. Consistently, actin polymerization is inhibited at sites of CynA accumulation, thereby restricting protrusions to the opposite edge. We suggest that the mutual antagonism between CynA and regions of responsiveness creates a positive feedback loop that restricts CynA to the rear and contributes to the establishment of the cell axis.

KEYWORDS:

Dictyostelium; asymmetry; chemotaxis; polarity; protein localization

PMID:
26130809
PMCID:
PMC4517219
DOI:
10.1073/pnas.1509098112
[Indexed for MEDLINE]
Free PMC Article

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