Fig. 1.

(a) Originally proposed structure of Densin-180. In homology to the domain structure of GpIbα, Densin-180 was proposed as a transmembrane domain (TMD) protein with a large extracellular area containing the leucine-rich repeats (LRRs) domain and a Mucin-homolog domain, while the intracellular part features a PDZ (Densin-180) and an Abp-binding domain (Abp; GpIbα), respectively (Apperson et al. 1996). (b) In vivo phosphorylation sites on Densin-180. Clusters of Ser/Thr phosphorylation (black) and two sites of Tyr phosphorylation (grey) (http://www.phosphosite.org; Trinidad et al. 2006; Munton et al. 2007; Rikova et al. 2007; Trinidad et al. 2008) were found N-terminal of the originally proposed single transmembrane domain. These phosphorylation sites are incompatible with the the original topology shown in (a). Numbering is for murine sequence uniprot Q80TE7-1. (c) Summary of domains on Densin-180. The hallmark LRRs, PDZ and LAP-specific domains domains at the N and C-terminal segments place Densin-180 in the LAP protein family (Santoni et al. 2002), which otherwise consists only out of all-intracellular members. The N-terminal palmitoylation (Izawa et al. 2008) positioned in analogy to Erbin (zig-zag line; anchors the N-terminus of Densin-180 to the membrane). The region containing clusters of phosphorylation shown in (b) is highlighted in blue. The cytoplasmic binding areas of rat Densin-180 for CamkIIα and α-Actinin are indicated, as are the areas of human Densin-180 binding to β-Catenin, δ-Catenin, Maguin- 1, and Shank (Strack et al. 2000; Walikonis et al. 2001; Izawa et al. 2002; Ohtakara et al. 2002; Quitsch et al. 2005; Robison et al. 2005; Heikkila et al. 2007). (d) Revised topology for Densin-180. All-intracellular and membrane-anchored topology of Densin-180.