Ced-12

CED-12 (Cell Death Abnormality Protein-12) is a cytoplasmic, PH-domain containing adaptor protein found in Caenorhabditis elegans and Drosophila melanogaster.

[3][4] Researchers also noted direct protein-protein interactions between CED-12 and CED-10 (C. elegans homolog for Rac1), a Rac-GTPase (energy-dependent protein found used for cytoskeletal rearrangements among other functions).

CED-10 is a RAC-GTPase protein that is directly responsible for the rearrangement of the actin cytoskeleton that initiates phagocytosis.

[11] The second pathway occurs when the CED-2/CED-5/CED-12 ternary structure form a GEF (guanine nucleotide exchange factor) with CED-10, which promotes the binding of a GTP energy molecule in order to activate the GTP-dependent CED-10.

[13] As C. elegans develops, the distal cells undergo a series of migrations in order to complete morphological changes, which define both gonad shape and size.

[12] This process occurs when integrins on the surface of the distal tip cells meet chemoattractants located on the extracellular matrix.

[12] CED-12 and CED-2 form the GEF-trio with CED-5 and activate the CED-10 Rac-GTPase in order to rearrange the actin cytoskeleton and promote the forward propagation of the distal tip cells.

A cartoon drawing depicting the apoptotic phagocytosis process. The apoptotic cell releases signals which are recognized by a neighbouring cell. The cell recognizing the signal activates CED-12 (pictured as light blue half moon crescent), CED-2 and CED-5, which form a ternary structure that activates CED-10. CED-10 activates actin cytoskeleton remodelling, causing phagocytosis of the dying cell.
(A) A simplified graphical representation of the protein domains for DOCK2 (mammalian homolog to CED-5) and ELMO1 (mammalian homolog for CED-12). On DOCK2/CED-5, the SH3-domain that binds to ELMO1/CED-12 is shown as a blue rectangle. On ELMO1, Proline-Rich regions, indicated by PH, are in light-blue. These indicate the regions in which ELMO1/CED-12 and DOCK2/CED-5 interact when forming a complex. (B) A crystalline 3D-representation of the heterodimer structure between DOCK2/CED-5 and ELMO1/CED-12. On the right is the same crystalline structure rotated 90°. NOT SHOWN: CrkII/CED-2 in the ternary structure with DOCK2/CED-5 and ELMO1/CED-12