Publications by authors named "B Fakler"

Article Synopsis
  • AJAP1 is a protein linked to brain diseases and is found in neurons, specifically in dendrites, where it plays a role in recruiting GABA type B receptors (GBRs) to presynaptic sites.
  • Several genetic variants of AJAP1, including the p.(W183C), have been associated with epilepsy and neurodevelopmental disorders, particularly affecting its ability to bind GBRs.
  • Mice lacking functional AJAP1 showed decreased levels of presynaptic GBRs, leading to impaired synaptic inhibition and plasticity, highlighting the importance of AJAP1 in regulating neurotransmitter release.
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GABA receptors (GBRs), the G protein-coupled receptors for GABA, regulate synaptic transmission throughout the brain. A main synaptic function of GBRs is the gating of Cav2.2-type Ca channels.

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Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents.

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The mitochondrial inner membrane plays central roles in bioenergetics and metabolism and contains several established membrane protein complexes. Here, we report the identification of a mega-complex of the inner membrane, termed mitochondrial multifunctional assembly (MIMAS). Its large size of 3 MDa explains why MIMAS has escaped detection in the analysis of mitochondria so far.

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The majority of mitochondrial precursor proteins are imported through the Tom40 β-barrel channel of the translocase of the outer membrane (TOM). The sorting and assembly machinery (SAM) is essential for β-barrel membrane protein insertion into the outer membrane and thus required for the assembly of the TOM complex. Here, we demonstrate that the α-helical outer membrane protein Mco6 co-assembles with the mitochondrial distribution and morphology protein Mdm10 as part of the SAM machinery.

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