Lecture 19- SNAREs II Flashcards
What happens if you inhibit membrane fusion in flies?
If you place flies at a restrictive temperature, you inhibit protein function
Flies can’t stand but can recover when brought back to a permissive temperature
What do Shibire flies encode?
Encodes the protein dynamin which is required for synaptic vesicles recycling
What do Comatose flies encode and therefore what is the consequence when the flies are exposed to a restrictive temperature?
Encodes NSF which is required for synaptic vesicle recycling
At restrictive temperatures, docked vesicles accumulate
What do Paralytic flies encode?
Encodes for a-subunit of voltage gates sodium channels
What phenotype occurs from a VAMP2 gene KO?
Die at birth. Loss of synaptic transmission
What phenotype occurs from a Syntaxin1A gene KO
No gross abnormalities and subtle defects in synaptic transmission
What phenotype occurs from a Syntaxin1B gene KO
Die at birth and reduced synaptic transmission
What phenotype occurs from a SNAP25 gene KO?
Die at birth and loss of synaptic transmission
What diseases can occur from a VAMP2 gene mutation
Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movement
What disease is caused by SNAP2b gene mutation?
Neurodevelopmental disorder with seizures, intellectual disability, severe speech delay and cerebellar ataxia
What diseases can occur from SNAP29 gene mutations?
Cerebral dysgenesis, neuropathy, ichthyosis and CEDNIK
What disease is caused by Syntaxin11 gene mutation?
FHL4
What is the molecular consequence of a VAMP2 heterozygous mutation?
Mutations effect the R SNARE coil domain of VAMP2
Mutation is S75P and slows the rate of lipid fusion
S75P mutation is classified as dominant negative mutation
Reduces the SNAREs ability to form complexes and be recycled
What is a dominant negative mutation?
A mutation whose gene products adversely affects the wild type gene product within the same cell
What is the molecular consequence of a syntaxin 11 mutation?
Patients with FHL4 have reduced levels of STX11 (Q SNARE) which causes defective degranulation from cytotoxic T-cells
