gpr-1 (C. elegans, UniProt Q95QJ7) - manual literature research

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Identity and paralogy

• GPR-1 (F22B7.13, 525 aa) is a TPR-like / GoLoco (GPR) motif protein, homologous to
  mammalian AGS3 / LGN (GPSM1/GPSM2) and Drosophila Pins. UniProt Q95QJ7 annotates a
  single GoLoco motif at residues 424-445 and an N-terminal TPR-like helical domain
  (InterPro IPR011990).
• GPR-1 and GPR-2 are "two closely related proteins" PMID:12730122. Their coding
  sequences are so similar that RNAi and antibodies do not distinguish them, so almost all
  functional data are reported for "GPR-1/2" PMID:16247027.

Molecular function: GoLoco GDI for G-alpha(i/o)

• The GoLoco/GPR motif binds GDP-bound Galpha(i/o) PMID:12730122;
  PMID:12750478.
• GDI activity on GOA-1 PMID:12814548 and on GPA-16 PMID:16162648.
• A GoLoco-insensitive GOA-1(N150I) mutant loses GPR-1 GoLoco binding and GDI sensitivity,
  confirming that the GDI activity depends on direct GoLoco-Galpha contact [PMID:18984596
  "abrogated interaction between the Caenorhabditis elegans Galpha subunit GOA-1 and the GPR-1
  GoLoco motif"; "we verified that GOA-1(N150I) is indeed resistant to GoLoco motif-mediated
  GDI activity"]. The GDI assays used a GPR-1/2 peptide (aa 423-461).
• RIC-8 (GEF) acts upstream; GPR-1/2 then engages free Galpha PMID:15479639.

Complex and cortical force generator

• GPR-1/2 associate with the NuMA-related coiled-coil protein LIN-5 and depend on it for
  localization PMID:12730122; PMID:12814548.
• Galpha-GPR-1/2-LIN-5 forms the ternary complex that anchors dynein at the cortex
  PMID:25548889; GPR-1/2 and LIN-5
  interact with LIS-1 and promote cortical dynein PMID:17922003.
• LIN-5-Galpha co-IP requires GPR-1/2 PMID:18234174.

Localization

• Cell cortex, posteriorly enriched during anaphase of the one-cell embryo in a PAR-dependent
  manner PMID:12750478; PMID:14534135. Anterior cortical enrichment during centration/rotation
  PMID:18234174. LET-99 inhibits lateral GPR-1/2 to give a bipolar pattern PMID:20421425.
  CSNK-1/PPK-1 (PIP2) control cortical levels PMID:18694560.
• Spindle / asters as well as cortex PMID:12730122; UniProt subcellular location.
• In EMS/P2, enriched at the P2-EMS contact; asymmetric only in P2 [PMID:21903670, abstract only,
  not cached].

Biological processes

• Generation of cortical pulling forces on astral microtubules that position the spindle
  asymmetrically in P-lineage divisions PMID:12750478; PMID:12814548.
• Anaphase spindle elongation / posterior displacement PMID:14534135.
• Pronuclear centration and rotation rates PMID:18234174.
• Not required for meiotic spindle rotation [PMID:19219036 abstract: "Spindle rotation during
  maternal meiosis is independent of GPR-1/2 and Galpha"].
• Signalling is receptor-independent PMID:12814548.

Open points

• The relative contributions of GPR-1 vs GPR-2 are unresolved because reagents target both.
• Whether the active force-generating species is Galpha-GDP-GPR-1/2 (GDI model) or Galpha-GTP
  generated by RIC-8 remains debated [PMID:18984596 discussion of the two competing models].