Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0005940 (
bone disease
)
7,459
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations in the human
TMEM16E
(
ANO5
) gene are associated both with the
bone disease
gnathodiaphyseal dysplasia (
GDD
; OMIM: 166260) and muscle dystrophies (OMIM: 611307, 613319). However, the physiological function of
TMEM16E
has remained unclear. We show here that human
TMEM16E
, when overexpressed in mammalian cell lines, displayed partial plasma membrane localization and gave rise to phospholipid scrambling (PLS) as well as non-selective ionic currents with slow time-dependent activation at highly depolarized membrane potentials. While the activity of wild-type
TMEM16E
depended on elevated cytosolic Ca
2+
levels, a mutant form carrying the
GDD
-causing T513I substitution showed PLS and large time-dependent ion currents even at low cytosolic Ca
2+
concentrations. Contrarily, mutation of the homologous position in the Ca
2+
-activated Cl
-
channel TMEM16B paralog hardly affected its function. In summary, these data provide the first direct demonstration of Ca
2+
-dependent PLS activity for
TMEM16E
and suggest a gain-of-function phenotype related to a
GDD
mutation.
...
PMID:Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia. 2912 9
