Fig. 7: Illustration summarizing the key findings of this work and the possible NAA60-related disease mechanism. | Nature Communications

Fig. 7: Illustration summarizing the key findings of this work and the possible NAA60-related disease mechanism.

From: Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

Fig. 7

NAA60 is established here as a PFBC-linked gene by loss of its N-terminal acetyltransferase activity in cases homozygous for NAA60 variants. A possible molecular mechanistic path through which loss of NAA60 function may cause primary familial brain calcifications (PFBCs) is shown. Loss of NAA60 function entails a lack of N-terminal acetylation (Ac-N) of several membrane proteins at the Golgi apparatus, possibly including some with critical function in brain phosphate homeostasis, such as SLC20A2. The impaired targeting or function of these non-Nt-acetylated NAA60 substrates may lead to the build-up of phosphate and calcium phosphate in the brains of patients with loss-of-function variants in NAA60, possibly via a pathway involving the phosphate importer SLC20A2. Parts of the figure were drawn by using elements modified with text, markings, and annotations from Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 (https://creativecommons.org/licenses/by/3.0/).

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