Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.

Clustering of Kv1 channels at the juxtaparanodal region (JXP) in myelinated axons depends on their association with the Caspr2/TAG-1 adhesion complex. The interaction between these channels and Caspr2 was suggested to depend on PDZ (PSD-95/Discs large/zona occludens-1) scaffolding proteins. Here, we show that at a subset of the JXP, PSD-93 colocalizes with Caspr2, K(+) channels and its related protein postsynaptic density protein-95 (PSD-95). The localization of PSD-93 and PSD-95 depends on the presence of Caspr2, as both scaffolding proteins failed to accumulate at the JXP in mice lacking either Caspr2 or TAG-1. In contrast, Caspr2 and K(+) channels still colocalized and associated in PSD-93, PSD-95 or double PSD-93/PSD-95 null mice. To directly evaluate the role of PDZ domain proteins in the function of Caspr2, we examined the ability of transgenic Caspr2 molecules lacking either their cytoplasmic domain (Caspr2dCT), or their PDZ-binding sequence (Caspr2dPDZ), to restore Kv1 channel clustering in Caspr2 null mice. We found that while Kv1 channels were distributed throughout internodes in nerves expressing Caspr2dCT, they were clustered at the JXP in axons expressing a full-length Caspr2 (Caspr2FL) or the Caspr2dPDZ transgene. Further proteomic analysis revealed that Caspr2 interacts with a distinct set of scaffolding proteins through its PDZ- and protein 4.1-binding sequences. These results demonstrate that while the molecular assembly of the JXP requires the cytoplasmic domain of Caspr2, its carboxy-terminal PDZ-binding motif is dispensable for Kv1 channel clustering. This mechanism is clearly distinct from the one operating at the axon initial segment, which requires PSD-93 for Kv1 channel clustering.

Pubmed ID: 19109503 RIS Download

Mesh terms: Animals | Binding Sites | Cell Adhesion Molecules, Neuronal | Contactin 2 | Gene Expression Regulation | Guanylate Kinases | Hemagglutinins | Humans | Intracellular Signaling Peptides and Proteins | Mass Spectrometry | Membrane Proteins | Mice | Mice, Transgenic | Mutation | Nerve Fibers, Myelinated | Nerve Tissue Proteins | Protein Structure, Tertiary | Sciatic Nerve | Shaker Superfamily of Potassium Channels | Sodium Channels

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS044916-03
  • Agency: NINDS NIH HHS, Id: R37 NS044916
  • Agency: NINDS NIH HHS, Id: R01 NS044916
  • Agency: NINDS NIH HHS, Id: R01 NS044916-05
  • Agency: NINDS NIH HHS, Id: NS044916
  • Agency: NINDS NIH HHS, Id: R01 NS044916-02
  • Agency: NINDS NIH HHS, Id: R01 NS044916-04

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.