chapter 2 - SCAMs Flashcards
2.1. [SCAMS] What are the functions of SCAMs at synapses?
Scams (synaptic cell adhesion molecules) are synaptic junctions organized by trans-synaptic cell-adhesin molecules bridging the synaptic cleft. Apart from connecting pre and post-synapses they also mediate trans-synaptic recognition and signaling processes that are essential for the establishment, specification, and plasticity of synapses.
2.2. [SCAMS] Define the role of SCAMs during synaptic formation stages (describe the stages as well) and synaptic function
Scams contribute to synaptic formation and function.
Stage 1. contact establishment: here pre and post-synapse establish contact through homophilic and heterophilic interactions between SCAMS to recognize the appropriate synaptic partners
Stage 2. recruitment of synaptic vesicles: once contact is established, synaptic vesicles are recruited. Here SCAMs regulate physical cell-cell adhesion and serve as anchor proteins to cluster or recruit receptors or components of the pre-and post-synaptic signaling machinery
stage 3. functional specification: molecular components of synapses are organized resulting in the functionality of the synapse
stage 4. synaptic plasticity: SCAMs may contribute to structural and functional changes in activity-dependent adaptive events (plasticity)
2.3. [SCAMS] What are the examples of SCAMs and their functional domains?
Adhesive function of scams is based on a limited number of extracellular domains , often assembled into repeat units.
SCAMs domains are
1- lamin A, neurexins (alpha and beta) and sex hormone binding protein (LNS)
2- neuroligins
both implicated in
schizophrenia and autism
3- immunoglobulin (lg)-domain proteins (e.g. synCAM) - usually homophilic, usually also contain fibronectin III domains - both heterophilic and homophilic
4- receptor phosphotyrosine kinases (phosphorylate) and phosphatases (dephosphorylates)
5- leucine-rich repeat proteins (LRR)
6-cadherin domains - always occur in multiple copies connected by a linker that binds 2-3 ca2+ ions. Usually homophilic.
Cadherins:
* influence early synapse development and impact synaptic plasticity
contain 5 extracellular cadherin repeat domains (EC1-5), with the N-terminal EC1 domain mediating adhesion in trans
* e.g. N-cadherin modulate synaptic function
NCAM: regulate synaptic plasticity
SynCAMs: synaptic cell adhesion molecules: organize excitatory synases
* contain 3 extracellular IgG domains, a single transmembrane region, and intracellular FERM- and PDZ-domain-binding motifs
SALMs: synaptic cell adhesion-like molecules: cluster post-synaptic plasticity
* single-pass membrane proteins with N-terminal LRR domain, a single Ig domain and fibronectin IlI domain, a transmembrane region and a cytoplasmic tail
* vertebrates contain 5 SALM genes
2.4. [SCAMS] draw SCAMs to illustrate how they function
see figures.
Functions of SCAMs have been discovered thanks to knock out animal models. Rodents wit the KO alpha Nrx suggest that alpha neurexin and neuroligin coordinate the recruitment of ca2+ channels and components of the release machinery, They also show reduced neurotransmitter release and that neurexin ligands do not act as synaptic glues but as activity-dependent regulators of synapse function - if disrupted they’re not essential for synaptic transmission however they affect its efficacy (e.g- less nt release probability, less ca2+)
Cadherins:
* influence early synapse development and impact synaptic plasticity
contain 5 extracellular cadherin repeat domains (EC1-5), with the N-terminal EC1 domain mediating adhesion in trans
* e.g. N-cadherin modulate synaptic function
NCAM: regulate synaptic plasticity
SynCAMs: synaptic cell adhesion molecules: organize excitatory synases
* contain 3 extracellular IgG domains, a single transmembrane region, and intracellular FERM- and PDZ-domain-binding motifs
SALMs: synaptic cell adhesion-like molecules: cluster post-synaptic plasticity
* single-pass membrane proteins with N-terminal LRR domain, a single Ig domain and fibronectin IlI domain, a transmembrane region and a cytoplasmic tail
* vertebrates contain 5 SALM genes
2.5 [SCAMS] Make a schematic drawing to illustrate neurexin-neuroligin interactions. Indicate and name the different functional domains.
How are these type of molecules called? What is the function of neurexin-neuroligin interactions?
-After answering, still look at the two slides containing info - not everything is written in the answer
Schematic drawing: slide 19. Neurexins and neuroligins are synaptic cell adhesion molecules.
Functional domains: extracellularly, a-neurexins contain 6 LNS (Lamin A, neurexin and sex-hormone-binding protein domains) domains with 3 interspersed EGF-like domains;
beta-neurexins only contain a single LNS domain. Intracellularly, the short cytoplasmic tails of neurexins contain PDZ-domain binding sequences that bind to intracellular proteins.
Neuroligins: their extracellular sequence contains an esterase-like domain that forms a constitutive dimer. Cytoplasmic neuroligin tails contain a PDZ-domain-binding sequences (and a tyrosine-based motif)
Neurexins bind to neuroligins to form trans-synaptic cell adhesion complexes, using the sixth LNS domain of a-neurexin and the single LNS domain of 6-neurexin.
Neurexin-neuroligin interactions are thought to have vital functions in organizing synapses, e.g. recruitment of calcium channels and components of the release machinery to presynaptic active zones.
