Healthcare and Medicine Reference
In-Depth Information
A
MuSK
Laminin
Agrin
AChR
a -Dystroglycan
MASC
RATL
b
P
rapsyn
P
P
B
FIGURE 8.20 Agrin binds to a receptor complex, and MuSK is required for clustering. A. The schematic
shows that Agrin activates a receptor complex that includes muscle-specific kinase (MuSK) and an uniden-
tified accessory protein (MASC). The intracellular peripheral membrane protein, Rapsyn, is required for the
Agrin-mediated MuSK activation to produce AChR phosphorylation, and it participates in receptor cluster-
ing. There are other Agrin binding sites, including laminin and a-dystroglycan. Laminin has been shown to
induce AChR clusters independent of MuSK signaling. B. In wild-type mice (+/+), AChRs aggregate at the
nerve-muscle junction (merged), but in MuSK-deficient mice (MuSK-/-) there is no clustering and the post-
synaptic site does not differentiate. (Adapted from Lin et al., 2001, Nature 410: 1057-1064)
RECEPTOR CLUSTERING
SIGNALS IN THE CNS
mRNA has been detected in the brains of embryonic
rats and chicks, and four splice variants of Agrin are dis-
tributed throughout the adult rat brain (Rupp et al.,
1991; Tsim et al., 1992; Ferns et al., 1992). However, dif-
fering results have been reported for an influence of
Agrin on synaptogenesis in the CNS (Serpinskaya et al.,
1999; Bose et al., 2000). Therefore, the search for receptor
Since receptor clustering is the most identifiable
postsynaptic feature of central synapses, it is reasonable
to ask whether Agrin-like molecules play a role. Agrin
 
 
Search Pocayo ::




Custom Search