RT Journal Article
SR Electronic
T1 Axonal targeting of Caspr2 in hippocampal neurons via selective somatodendritic endocytosis
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 3403
OP 3413
DO 10.1242/jcs.050526
VO 122
IS 18
A1 Bel, Christophe
A1 Oguievetskaia, Ksénia
A1 Pitaval, Christophe
A1 Goutebroze, Laurence
A1 Faivre-Sarrailh, Catherine
YR 2009
UL http://jcs.biologists.org/content/122/18/3403.abstract
AB Contactin-associated protein 2 (Caspr2) is a neuronal membrane protein that is mutated in autism and related disorders. Although it is highly enriched at juxtaparanodes of Ranvier where it is essential for Shaker-type K+ channel clustering, little is known about its function and regulation. In the present study, we examined the polarized expression of Caspr2 in hippocampal neurons using extracellular hemagglutinin (HA)-tagged Caspr2 constructs. We found that Caspr2 was targeted to the axonal surface, but colocalized with early endosomes in the somatodendritic compartment. The inhibition of endocytosis using a Dynamin-1 mutant or treatment with Dynasore prevented Caspr2 internalization from the dendrites and cell body. We identified a short sequence included into the 4.1B-binding domain that is required for the endocytosis of Caspr2. This sequence contains a protein kinase C (PKC) substrate motif on Thr1292, and point mutation of this residue or treatment with a PKC inhibitor prevented the somatodendritic internalization of Caspr2. Thus, the PKC-dependent trafficking of Caspr2 underlies its polarized expression in hippocampal neurons.