Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The traffic of Kv4 K+ channels is regulated by the potassium channel interacting proteins (KChIPs). Kv4.2 expressed alone was not retained within the ER, but reached the Golgi complex. Coexpression of KChIP1 resulted in traffic of the channel to the plasma membrane, and traffic was abolished when mutations were introduced into the EF-hands with channel captured on vesicular structures that colocalized with KChIP1(2-4)-EYFP. The EF-hand mutant had no effect on general exocytic traffic. Traffic of Kv4.2 was coat protein complex I (COPI)-dependent, but KChIP1-containing vesicles were not COPII-coated, and expression of a GTP-loaded Sar1 mutant to block COPII function more effectively inhibited traffic of vesicular stomatitis virus glycoprotein (VSVG) than did KChIP1/Kv4.2 through the secretory pathway. Therefore, KChIP1seems to be targeted to post-ER transport vesicles, different from COPII-coated vesicles and those involved in traffic of VSVG. When expressed in hippocampal neurons, KChIP1 co-distributed with dendritic Golgi outposts; therefore, the KChIP1 pathway could play an important role in local vesicular traffic in neurons.
 ...
PMID:Traffic of Kv4 K+ channels mediated by KChIP1 is via a novel post-ER vesicular pathway. 1626 Apr 97

The KChIPs (K(+) channel-interacting proteins) are EF hand-containing proteins required for the traffic of channel-forming Kv4 K(+) subunits to the plasma membrane. KChIP1 is targeted, through N-terminal myristoylation, to intracellular vesicles that appear to be trafficking intermediates from the ER (endoplasmic reticulum) to the Golgi but differ from those underlying conventional ER-Golgi traffic. To define KChIP1 vesicles and the traffic pathway followed by Kv4/KChIP1 traffic, we examined their relationship to potential SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins mediating the trafficking step. To distinguish Kv4/KChIP1 from conventional constitutive traffic, we compared it to the traffic of the VSVG (vesicular-stomatitis virus G-protein). Expression of KChIP with single or triple EF hand mutations quantitatively inhibited Kv4/KChIP1 traffic to the cell surface but had no effect on VSVG traffic. KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7 (vesicle-associated membrane protein 7), but not with the components of two other ER-Golgi SNARE complexes. siRNA (small interfering RNA)-mediated knockdown of Vti1a or VAMP7 inhibited Kv4/KChIP1traffic to the plasma membrane in HeLa and Neuro2A cells. Vti1a and VAMP7 siRNA had no effect on VSVG traffic or that of Kv4.2 when stimulated by KChIP2, a KChIP with different intrinsic membrane targeting compared with KChIP1. The present results suggest that a SNARE complex containing VAMP7 and Vti1a defines a novel traffic pathway to the cell surface in both neuronal and non-neuronal cells.
 ...
PMID:A VAMP7/Vti1a SNARE complex distinguishes a non-conventional traffic route to the cell surface used by KChIP1 and Kv4 potassium channels. 1913 72