Biomedical Engineering Reference
In-Depth Information
Cadherin
EGF
Laminin G
HRM
GPS
Figure 7.1 Schematic representation of the Celsr1 protein. The extracellular domain in-
cludes nine cadherin repeats, six epidermal growth factor (EGF)-like domains, two lam-
inin G repeats, one hormone receptor motif (HRM), and a G-protein-coupled receptor
proteolytic site (GPS). In contrast to typical cadherins which are single-pass proteins,
Celsr1-3 cadherins are anchored to the plasma membrane by seven transmembrane
domains. The cytoplasmic tail varies in size and is poorly conserved among the three
Celsrs.
These receptors are thought to be natural chimeras of cell adhesion proteins
and signaling receptors, able to convert cell-cell communication cues into
intracellular signals. Studies of the latrotoxin receptor latrophilin, a member
of LNB-GPCR, showed that cleavage at the GPS occurs intracellularly.
However, the N-terminal (cell adhesion domain) and C-terminal (GPCR)
fragments remain associated by noncovalent bonds at the plasma membrane
(
Krasnoperov et al., 2002; Volynski et al., 2004
). It is not clear yet whether
cleavage at the GPS occurs in Celsr1-3 proteins (see below). In addition to
cadherin and EGF-like repeats which confer adhesive properties and
facilitate cell-cell communication, the extracellular domain of Celsr1-3
