L11 - SNAREs 2

Question 1

What kind of mutation inhibits fusion of vesicles in mammals?

Answer 1

Temperature related mutations, vesicles start to accumulate

Question 2

How can mutations in these SNARE proteins lead to disease:
VAMP2 –
SNAP29 –
Syntaxin11 –

Answer 2

VAMP2 – expressed in the brain. Mutation gives neurodevelopmental disorder with hypotonia and autistic features
SNAP29 – expressed in other tissues like the skin. Mutation results in cerebral dysgenesis, neuropathy, palmoplantar keratoderma syndrome
Syntaxin11 – expressed in immune system. Mutations cause familial hemophagocytic lymphohistiocytosis (FLH4)

Question 3

What are the effects of VAMP2 mutations?

Answer 3

-Cause serious neurodevelopmental disorder
-Characterised by axial hypotonia, intellectual disability, and autistic features
-Uncoordinated movements

Question 4

What are effects of the disease FLH4?

Answer 4

-Rare disease of the immune system (predominantly effects infants)
-Over proliferation of T cells, natural killer cells, B cells and macrophages
-T cells kill infected cells by secreting cytotoxic granules

Question 5

What mutation other than Syntaxin11 causes FLH4?

Answer 5

Mutation in Munc18-2

Question 6

What do the clostridia toxins (clostridia tetani and clostridia botulism) do?

Answer 6

They cleave SNAREs

Question 7

Which SNARES do the botulinum toxin bind to? (2)

Answer 7

-SNAP25
-Syntaxin

Question 8

What are the clinical uses for Botulinum neurotoxins? (4)

Answer 8

-Cosmetic uses
-Used for Parkinson’s for over salivating
-Interest into using these to treat chronic pain
-Used to treat: strabismus, blepharospasm, cervical dystonia, axially hyperhidrosis, GI tract disorders