Publications by authors named "Stefan H Gerber"
Article Synopsis
- Piccolo and bassoon are proteins found in nerve terminals whose roles in synaptic function are still unclear; researchers created various models of mice with altered levels of piccolo to study its effects.
- While these mutant mice were viable, the complete knockout of piccolo led to increased mortality after birth, but traditional tests did not show significant changes in synaptic function in cultured neurons.
- However, when piccolo and bassoon were both reduced, there was notable disruption in the clustering of synaptic vesicles, suggesting these proteins may redundantly assist in this process rather than directly influencing neurotransmitter release.
Article Synopsis
- During synaptic vesicle fusion, syntaxin-1 has two forms: a "closed" conformation that is outside the SNARE complex and an "open" conformation that is part of the SNARE complex.
- Research using specially modified mice showed that only having the open form of syntaxin-1B led to seizures and other synaptic issues.
- The study concluded that the closed form of syntaxin-1 plays a crucial role in regulating when synaptic vesicle fusion begins, enabling effective communication between neurons.
Article Synopsis
- The study investigates how nerve growth factor (NGF) affects cardiac norepinephrine levels in heart failure, where the normal reuptake of norepinephrine is impaired.
- Researchers injected NGF into the stellate ganglia of rats with induced heart failure, finding that it restored depleted cardiac norepinephrine stores and improved norepinephrine uptake.
- The results suggest that NGF may help reduce excessive cardiac sympathetic activation, indicating its potential as a new treatment approach for heart failure.
A conformational switch in the Piccolo C2A domain regulated by alternative splicing.
Nat Struct Mol Biol
January 2004
Article Synopsis
- - C2 domains are calcium-binding modules, and the Piccolo protein has a unique C2A domain that shows low calcium affinity and can change shape and form dimers in the presence of calcium.
- - Removing a specific nine-residue sequence through alternative splicing increases calcium affinity but eliminates the domain's ability to change shape and dimerize.
- - The structural analysis of the longer variant of the Piccolo C2A domain suggests that the absence of the nine residues prevents necessary rearrangements, revealing new insights into how alternative splicing can modify protein function.
Article Synopsis
- The study investigates how the C2 domain of cytosolic phospholipase A2 (cPLA2) is targeted to the Golgi and endoplasmic reticulum (ER) when intracellular calcium levels rise.
- It compares the targeting mechanisms of the cPLA2 C2 domain with those of synaptotagmin 1 C2A and protein kinase Calpha C2 in kidney cells.
- Findings indicate that certain calcium binding loops in the cPLA2 C2 domain are crucial for its specific targeting to the Golgi/ER, distinguishing it from other C2 domains.
Synaptotagmin 1, a Ca2+ sensor for fast synaptic vesicle exocytosis, contains two C2 domains that form Ca2+-dependent complexes with phospholipids. To examine the functional importance of Ca2+ binding to the C2A domain of synaptotagmin 1, we studied two C2A domain mutations, D232N and D238N, using recombinant proteins and knock-in mice. Both mutations severely decreased intrinsic Ca2+ binding and Ca2+-dependent phospholipid binding by the isolated C2A domain.
View Article and Find Full Text PDFPhosphatidylinositol (PtdIns) 4-kinases catalyze the conversion of PtdIns to PtdIns 4-phosphate, the major precursor of phosphoinositides that regulates a vast array of cellular processes. Based on enzymatic differences, two classes of PtdIns 4-kinase have been distinguished termed Types II and III. Type III kinases, which belong to the phosphatidylinositol (PI) 3/4-kinase family, have been extensively characterized.
View Article and Find Full Text PDFArticle Synopsis
- C(2)-domains, like the C(2)A-domain of synaptotagmin I, are crucial for binding to phospholipid bilayers in a Ca(2+)-dependent manner, crucial for processes like exocytosis.
- The binding mechanism involves both electrostatic interactions that respond to ionic strength and hydrophobic interactions facilitated by specific amino acids, notably methionine 173.
- This study suggests that the phospholipid binding process employs a multimodal mechanism that’s essential for the function of synaptotagmin in exocytosis.
Article Synopsis
- Regulated exocytosis is vital for intercellular communication, particularly in hormone and neurotransmitter release, and is typically initiated by calcium.
- Recent studies have focused on two main aspects: the membrane fusion process facilitated by SNARE proteins and munc18-like proteins, which are crucial for this reaction.
- The role of synaptotagmins, a family of calcium sensors, is also explored as a key factor that triggers exocytosis, contributing to a deeper understanding of these complex molecular mechanisms.