The GoLoco Motif: Heralding a New Tango Between G Protein Signaling and Cell Division

  1. Randall J. Kimple,
  2. Francis S. Willard and
  3. David P. Siderovski
  1. Department of Pharmacology Lineberger Comprehensive Cancer Center Unc Neuroscience Center The University of North Carolina at Chapel Hill Chapel Hill NC 27599-7365 USA
  1. DPS. E-mail dsiderov{at}; fax 919-966-5640.


The Gα and Gβγ components of heterotrimeric G proteins, typically associated with cell-surface receptor signaling, also partake in the macromolecular interactions that underlie cell polarity and cell division. Proteins with Gα-binding GoLoco motifs, such as Drosophila melanogaster Pins (for Partner of Inscuteable) and its mammalian counterpart LGN, participate in multi-protein complexes that maintain cellular asymmetry and orderly segregation of chromosomal content and daughter cell bodies. The GoLoco motif was recently identified as a selective Gα-binding partner: the GoLoco–Gα interaction can displace Gβγ and inhibit guanine nucleotide release from the bound Gα subunit. Recent x-ray crystallographic studies suggest ways in which GoLoco-motif peptides may modulate heterotrimeric G protein signaling. Such peptides could be exploited to help dissect the signals that underpin cell polarity and cell division processes.

Graphic Heterotrimeric G proteins regulate signaling pathways downstream of plasma membrane-bound receptors. Several mechanisms have been discovered that promote the separate effector functions of the Gα and the Gβγ subunits. Recent efforts have identified GoLoco motif-containing proteins as Gα-associated proteins that can regulate the reassociation of Gα to Gβγ, and that might effect signal transduction on their own. In what physiological processes are these proteins involved?

| Table of Contents