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MemBrain – Membrane proteins in the brain

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Henriette Aksnes
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Alessia Caiella
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Topic

We study membrane proteins with crucial functions in the brain. The group’s direction spurred from the PI’s previous work on the enzyme Na-acetyltransferase 60 (NAA60). This protein catalyzes N-terminal acetylation (Nt-acetylation), a highly abundant protein modification with vital roles (1, 2). What sets NAA60 apart from other N-terminal acetyltransferases is its unique localization to intracellular membranes and its preference for acting on membrane proteins (3, 4).

Furthermore, NAA60 plays a significant role in preserving the structural integrity of the Golgi apparatus, potentially holding a crucial function within the secretory pathway (3). The secretory pathway is responsible for the synthesis, alteration, and sorting of membrane and secretory proteins to specific intracellular organelles, the cell surface, or the extracellular environment. This pathway holds particular significance in the realm of neurobiology and has been linked to neurodegenerative conditions.

Interestingly, we recently found pathogenic variants of NAA60 to be causative of a hereditary neurodegenerative disease (5).

Nt-acetylation has diverse effects on the receiving protein and serve vital roles in the human body (2). However, when it comes to proteins of the secretory pathway, the molecular consequences and physiological importance of Nt-acetylation stand as major unresolved questions. The group’s overall objective is to study membrane proteins, and their influence by modifications such as Nt-acetylation, in neurodegenerative disease.

 

Methods

We specialize in cell- and molecular biology techniques. The group has competence in methods such as:

- Fluorescent microscopy (wide-field, confocal, STED, TIRF).

- Live-cell imaging

- Digital holographic imaging and analysis

- 3D cell cultures

- Human neuronal cultures

- CRSPR/Cas9 cell line editing

- HAP1 cell model and quality control

- Secretory pathway assays

- Flow cytometry

- Protein analysis, e.g. immunoblot and mass spectrometry

- Yeast Saccharomyces cerevisiae

 

Interested in collaborating? Please get in touch.