Cell-cell communication Flashcards

Question

What is cardiac dysfunction?

Answer 1

Mutations in heart Na+ and K+ channels lead to cardiac channelopathy called LQTS

Answer 2

Loss of function in KCNQ1 which codes for slow K channel

Answer 3

Loss of function in KCNH2 which codes for rapid K channel

Answer 4

Gain of SCN5A gene which encodes for sodium channel, causing failed inactivation of channel

Answer 5

Nucleotide change means different codon and different amino acid

Answer 6

Missense mutations cause increase of function of KCNH2 in SQTS1, KCNQ1 in SQTS2 and KCNJ2 in SQTS3

Answer 7

Monomeric GTP-binding protein

Answer 8

- Most RTKs activate Ras - a monomeric GTP-binding protein (GTP-ase) - RTKs linked to enzymes - the enzyme is a kinase which phosphorylate molecules - Tyrosine kinases add phosphate to tyrosine - Ligand binds to receptor - often receptor is dimer and sometimes tetramer - Binding of ligand stabilizes dimer, receptors phosphorylate each other and this allows adaptor molecules to bind which determine downstream signaling - Adaptor molecules recruit Ras guanine exchange factor (GEF) to catalyze conversion of Ras from inactive GDP bound form to active GTP bound form - This then signals to other molecules - Most RTKs activate Ras signaling molecule

Answer 9

Breast cancer - increased signalling downstream of RTLK

Answer 10

Tyrosine kinase inhibitors

Answer 11

Colorectal cancer

Answer 12

Breast cancer

Answer 13

- Absence of ligand when GPCR is inactive - GPCR = G-protein coupled receptors - GPCRs bind to G proteins which are a trimeric protein, alpha, beta and gamma subunits - G protein bind GDP when GPCR is inactive but binds GTP when active, also causes trimeric protein to split (alpha and beta/gamma subunits) and two signals - Alpha, beta/gamma unit and G-protein all exert signals - G protein hydrolyses GTP to GDP to inactivate GPCR

Answer 14

- G protein hydrolyses GTP to GDP to inactivate GPCR - E.g. target protein is adenyl cyclase - ATP -(adenyl cyclase)→ cAMP -(cAMP phosphodiesterase)→ 5'AMP - Alpha subunit hydrolyses GDP to GDP and then reassembles with beta/gamma subunits

Answer 15

Severe water loss, vomiting and muscle cramps

Answer 16

Vibrio cholera

Answer 17

- Cholera toxin binds to enterocytes (epithelial cells in GIT) and the toxin enters the cell by endocytosis - Toxin formed form A and beta units (B assists body entry) - The A subunit stimulates fluid secretion by activating cAMP formation - A subunit activates Gsa - A subunit catalyses transfer of ADP ribose from NAD to arginine group on alpha subunit of G-alpha-S sub molecules - ADP ribosylation inhibits the ability of G-alpha-S to hydrolyse GTP and inactivate the molecule - this means that G protein is 'locked' in active position and this maintains a persistent activation of adenylate cyclase and formation of cAMP which in turn activates protein kinase A (PKA) - G protein is in GTP-bound form - Stimulates adenylate cyclase - cAMP produced activates PKA - CFTR is phosphorylated and activated - Efflux of Cl- ions (and sodium ions and water) - Due to charge across membrane, sodium ions pass out of cell and water is lost due to change in osmotic gradient

Answer 18

- Decrease in production of G proteins: pseudohypoparathyroidism (genetic loss of G(s) protein a subunits results in no response to parathyroid hormone) - Decreased signal initiation: whooping cough (pertussis)(a bacteria toxin adds ADP-ribose to the receptor-binding C-terminal tail of G(i) protein alpha subunits, causing reduced responsiveness of G proteins to receptor activation - Increased signal initiation: essential hypertension - mutations in G protein beta subunits - Defective signal termination