Molecular view of ER membrane remodeling by the Sec61/TRAP translocon.

Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon-associated protein complex (TRAP), yet the mechanism by which TRAP assists in polypeptide translocation remains unknown.

MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus.

Balanced synaptic inhibition, controlled by multiple synaptic adhesion proteins, is critical for proper brain function. MDGA1 (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu [MAM] domain-containing glycosylphosphatidylinositol anchor protein 1) suppresses synaptic inhibition in mammalian neurons, yet the molecular mechanisms underlying MDGA1-mediated negative regulation of GABAergic synapses remain unresolved. Here, we show that the MDGA1 MAM domain directly interacts with the extension domain of amyloid precursor protein (APP).

Crystallization and low-resolution structure solution of the SALM3-PTPσ synaptic adhesion complex.

Synaptic adhesion molecules are major organizers of the neuronal network and play a crucial role in the regulation of synapse development and maintenance in the brain. Synaptic adhesion-like molecules (SALMs) and leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-PTPs) are adhesion protein families with established synaptic function. Dysfunction of several synaptic adhesion molecules has been linked to cognitive disorders such as autism spectrum disorders and schizophrenia.

Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPσ.

Synaptic adhesion molecules play an important role in the formation, maintenance and refinement of neuronal connectivity. Recently, several leucine rich repeat (LRR) domain containing neuronal adhesion molecules have been characterized including netrin G-ligands, SLITRKs and the synaptic adhesion-like molecules (SALMs). Dysregulation of these adhesion molecules have been genetically and functionally linked to various neurological disorders.

Inhibitor screening assay for neurexin-LRRTM adhesion protein interaction involved in synaptic maintenance and neurological disorders.

Synaptic adhesion molecules, including presynaptic neurexins (NRXNs) and post-synaptic leucine-rich repeat transmembrane (LRRTM) proteins are important for development and maintenance of brain neuronal networks. NRXNs are probably the best characterized synaptic adhesion molecules, and one of the major presynaptic organizer proteins. The LRRTMs were found as ligands for NRXNs.

The structure of SALM5 suggests a dimeric assembly for the presynaptic RPTP ligand recognition.

Synaptic adhesion molecules play a crucial role in the regulation of synapse development and maintenance. Recently, several families of leucine-rich repeat (LRR) domain-containing neuronal adhesion molecules have been characterised, including netrin-G ligands, LRRTMs and the synaptic adhesion-like molecule (SALM) family proteins. Most of these are expressed at the excitatory glutamatergic synapses, and dysfunctions of these genes are genetically linked with cognitive disorders, such as autism spectrum disorders and schizophrenia.