August 1, 2003
View Full PaperA Conserved Domain in Axonal Targeting of Kv1 (Shaker) Voltage-Gated Potassium Channels
Structured PICO
P
Population
Cellular models expressing Kv1 (Shaker) voltage-gated potassium channels, CD4, and dendritic transferrin receptor
I
Intervention
Fusion of T1 tetramerization domain to unpolarized CD4 or dendritic transferrin receptor; T1 mutations eliminating Kvbeta association
C
Comparator
Proteins without T1 fusion; wild-type T1 domain
O
Outcome
Axonal targeting and surface expression
The T1 tetramerization domain and its proper association with Kvbeta are essential for the axonal targeting of Kv1 voltage-gated potassium channels.
Abstract
Axonal voltage-gated potassium (Kv1) channels regulate action-potential invasion and hence transmitter release. Although evolutionarily conserved, what mediates their axonal targeting is not known. We found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 or dendritic transferrin receptor, T1 promoted their axonal surface expression. Moreover, T1 mutations eliminating Kvbeta association compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. Thus, proper association of Kvbeta with the Kv1 T1 domain is essential for axonal targeting.