Dock protein family in brain development and neurological disease

Abstract

The family of dedicator of cytokinesis (Dock), a protein family that belongs to the atypical Rho guanine nucleotide exchange factors (GEFs) for Rac and/or Cdc42 GTPases, plays pivotal roles in various processes of brain development. To date, 11 members of Docks have been identified in the mammalian system. Emerging evidence has suggested that members of the Dock family are associated with several neurodegenerative and neuropsychiatric diseases, including Alzheimer disease and autism spectrum disorders. This review summarizes recent advances on the understanding of the roles of the Dock protein family in normal and diseased processes in the nervous system. Furthermore, interacting proteins and the molecular regulation of Docks are discussed.

Keywords: Cdc42; ELMO; Rac; Rho GTPase; actin; axon; dedicator of cytokinesis; dendrite; guanine nucleotide exchange factor; neurite; synapse.

Figure 1. Schematic structure of different members of Dock protein family. Dock family proteins are divided into 4 subfamilies, Dock-A–D. Members of each subfamily and their alternate names are listed (MOCA, modifier of cell adhesion; PBP, presenilin-binding protein; Zir, zizimin-related). Structure of different domains, including SH3 (Src Homology 3), PH (pleckstrin homology), DHR (Dock homology region) 1, DHR2, and the proline-rich region (PxxP) are indicated.