W4 pre: Introduction to neuropeptides as regulators of physiological processes and whole-animal behaviour

What are neuropeptides?

peptides synthesised and released by neurons as intracellular signalling molecules

How large are neuropeptides?

3 - 40 residues

Where are neuropeptides derived from?

larger precursor proteins

Where are neuropeptides released from?

large dense core vesicles

What is release of neuropeptides triggered by?

long lasting but low frequency bouts of action potentials

Compared to neurotransmitters, how quickly do neuropeptides work and what distances do they they cover?

• more slowly

• larger distances

What are neuropeptides involved in?

mediating neuronal control/regulation of wide range physiological and behavioural processes (feeding/reproduction)

What kind of receptors do neuropeptides typically bind to?

G-protein coupled receptors

What can neuropeptides be evolutionarily traced back to?

common ancestor of the Bilatera

How are neuropeptides derived from precursor proteins?

cleavage by endopeptidases at dibasic or nonobasic sites

Give an example of an endopeptidase and describe its action

prohormone convertases (PC1 & PC2) cleave precursors at the C terminus of peptide bonds at dibasic (Lysine-Arganine) or monobasic (Arg) sites

Where does cleavage of neuropeptides from precursor proteins occur?

golgi apparatus

Describe the cleavage process of neuropeptide enkephalin from its precursor protein (2 points)

• prohormone convertase cleaves precursor at dibasic cleavage sites (lys-arg & lys-lys)

• carboxypeptidase E removes the basic residues that make up the cleavage site

List 3 post-translational modifications of neuropeptides

• C-terminal amidation & N-terminal pyroglutamate

• sulphation of tyrosine residues

• addition of disulphide bridges between cysteine residues

Discuss C-terminal amidation & N-terminal pyroglutamation (2 points)

• conversion of C-terminal glycine residue into an amide group

• conversion of N-terminal glutamine into pyroglutamate

Give an example of a

neuropeptide that undergoes C-terminal amidation & N-terminal pyroglutamation

thyrotropin releasing hormone

What is the benefit of C-terminal amidation & N-terminal pyroglutamation?

protects neuropeptide from from degradation by peptidases, increasing their half life when secreted

What peptidase is resisted by the addition of a C-terminal amide group?

carboxypeptidases

What peptidase is resisted by the addition of a N-terminal pyroglutamate group?

aminopeptidases

In which 2 neuropeptides do sulphation of tyrosine residues occur in and what’s its benefit?

• cholecytokinin

• gastrin

essential for their bioactivity

In which 2 neuropeptides do addition of disulphide bridges between cysteine residues occur in?

• vasopressin

• oxytocin

List 3 physiological levels that neuropeptides act on

• molecular/cellular

• neuronal circuit / systems

• behavioural/emotional