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2017 ; 6
(ä): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
The interactome of the copper transporter ATP7A belongs to a network of
neurodevelopmental and neurodegeneration factors
#MMPMID28355134
Comstra HS
; McArthy J
; Rudin-Rush S
; Hartwig C
; Gokhale A
; Zlatic SA
; Blackburn JB
; Werner E
; Petris M
; D'Souza P
; Panuwet P
; Barr DB
; Lupashin V
; Vrailas-Mortimer A
; Faundez V
Elife
2017[Mar]; 6
(ä): ä PMID28355134
show ga
Genetic and environmental factors, such as metals, interact to determine
neurological traits. We reasoned that interactomes of molecules handling metals
in neurons should include novel metal homeostasis pathways. We focused on copper
and its transporter ATP7A because ATP7A null mutations cause neurodegeneration.
We performed ATP7A immunoaffinity chromatography and identified 541 proteins
co-isolating with ATP7A. The ATP7A interactome concentrated gene products
implicated in neurodegeneration and neurodevelopmental disorders, including
subunits of the Golgi-localized conserved oligomeric Golgi (COG) complex. COG
null cells possess altered content and subcellular localization of ATP7A and CTR1
(SLC31A1), the transporter required for copper uptake, as well as decreased total
cellular copper, and impaired copper-dependent metabolic responses. Changes in
the expression of ATP7A and COG subunits in Drosophila neurons altered synapse
development in larvae and copper-induced mortality of adult flies. We conclude
that the ATP7A interactome encompasses a novel COG-dependent mechanism to specify
neuronal development and survival.