TY - JOUR
T1 - The septate junction protein caspr is required for structural support and retention of KCNQ4 at calyceal synapses of vestibular hair cells
AU - Sousa, Aurea D.
AU - Andrade, Leonardo R.
AU - Salles, Felipe T.
AU - Pillai, Anilkumar M.
AU - Buttermore, Elizabeth D.
AU - Bhat, Manzoor A.
AU - Kachar, Bechara
PY - 2009/3/11
Y1 - 2009/3/11
N2 - The afferent innervation contacting the type I hair cells of the vestibular sensory epithelia form distinct calyceal synapses. The apposed presynaptic and postsynaptic membranes at this large area of synaptic contact are kept at a remarkably regular distance. Here, we show by freeze-fracture electron microscopy that a patterned alignment of proteins at the calyceal membrane resembles a type of intercellular junction that is rare in vertebrates, the septate junction (SJ). We found that a core molecular component of SJs, Caspr, colocalizes with the K + channel KCNQ4 at the postsynaptic membranes of these calyceal synapses. Immunolabeling and ultrastructural analyses of Caspr knock-out mice reveal that, in the absence of Caspr, the separation between the membranes of the hair cells and the afferent neurons is conspicuously irregular and often increased by an order of magnitude. In these mutants, KCNQ4 fails to cluster at the postsynaptic membrane and appears diffused along the entire calyceal membrane. Our results indicate that a septate-like junction provides structural support to calyceal synaptic contact with the vestibular hair cell and that Caspr is required for the recruitment or retention of KCNQ4 at these synapses.
AB - The afferent innervation contacting the type I hair cells of the vestibular sensory epithelia form distinct calyceal synapses. The apposed presynaptic and postsynaptic membranes at this large area of synaptic contact are kept at a remarkably regular distance. Here, we show by freeze-fracture electron microscopy that a patterned alignment of proteins at the calyceal membrane resembles a type of intercellular junction that is rare in vertebrates, the septate junction (SJ). We found that a core molecular component of SJs, Caspr, colocalizes with the K + channel KCNQ4 at the postsynaptic membranes of these calyceal synapses. Immunolabeling and ultrastructural analyses of Caspr knock-out mice reveal that, in the absence of Caspr, the separation between the membranes of the hair cells and the afferent neurons is conspicuously irregular and often increased by an order of magnitude. In these mutants, KCNQ4 fails to cluster at the postsynaptic membrane and appears diffused along the entire calyceal membrane. Our results indicate that a septate-like junction provides structural support to calyceal synaptic contact with the vestibular hair cell and that Caspr is required for the recruitment or retention of KCNQ4 at these synapses.
UR - http://www.scopus.com/inward/record.url?scp=63849187806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63849187806&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4868-08.2009
DO - 10.1523/JNEUROSCI.4868-08.2009
M3 - Article
C2 - 19279247
AN - SCOPUS:63849187806
SN - 0270-6474
VL - 29
SP - 3103
EP - 3108
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 10
ER -