Disease Associated Mutations in KIR Proteins Linked to Aberrant Inward Rectifier Channel Trafficking.
Biomolecules
; 9(11)2019 10 25.
Article
en En
| MEDLINE
| ID: mdl-31731488
ABSTRACT
The ubiquitously expressed family of inward rectifier potassium (KIR) channels, encoded by KCNJ genes, is primarily involved in cell excitability and potassium homeostasis. Channel mutations associate with a variety of severe human diseases and syndromes, affecting many organ systems including the central and peripheral neural system, heart, kidney, pancreas, and skeletal muscle. A number of mutations associate with altered ion channel expression at the plasma membrane, which might result from defective channel trafficking. Trafficking involves cellular processes that transport ion channels to and from their place of function. By alignment of all KIR channels, and depicting the trafficking associated mutations, three mutational hotspots were identified. One localized in the transmembrane-domain 1 and immediately adjacent sequences, one was found in the G-loop and Golgi-export domain, and the third one was detected at the immunoglobulin-like domain. Surprisingly, only few mutations were observed in experimentally determined Endoplasmic Reticulum (ER)exit-, export-, or ER-retention motifs. Structural mapping of the trafficking defect causing mutations provided a 3D framework, which indicates that trafficking deficient mutations form clusters. These "mutation clusters" affect trafficking by different mechanisms, including protein stability.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Predisposición Genética a la Enfermedad
/
Canales de Potasio de Rectificación Interna
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Biomolecules
Año:
2019
Tipo del documento:
Article
País de afiliación:
Austria