Receptors in health & disease Flashcards
Why do single celled organisms need receptors?
Interact with their external environment, sense toxins, bind nutrients
Why do multicellular organisms need receptors?
Allows communication with extracellular environment
cell-cell contact
What are the 2 cell specific receptors?
contact-dependent
synaptic
What are the 2 cell type receptors?
paracrine
endocrine
What are the multiple receptor families?
G protein-coupled receptors
Enzyme-coupled receptors
Adhesion receptors
Pathogen recognition receptors
What are G protein-coupled receptors?
7 transmembrane domains
conformational changes by membrane spanning helices
helices interact with G proteins
increase in secondary messengers
How are G-protein-coupled receptors activated?
inactive - bound to GDP
bind ligand - conformational change - exchange of GTP
What is a diseases associated with GPCRs?
Parathyroid hormone receptor (PTHR)
regulates of calcium and phosphorous concentration
activation of particular alpha subunit > cAMP > constitutive receptor activation
leads to shortlimbed dwarfism
What is Grave’s diseases?
causes hyperthroidism via TSHR agonistic antibodies
excess generation of cAMP - weight loss, goitre
What is Hashimoto’s disease?
antagonistic antibodies
reduction in cAMP
weight gain, fatigue
What occurs in toxin activation of GPCRs?
cholera - activation of cAMP
Pertussis - prevents activation ia ADP-ribosylation, increase in cAMP
What phenotypes do non-germline defect give?
cafe-au-lait
fibrous dysplasia osteoblast dysfunction
What are Enzyme-coupled receptor tyrosine kinases?
signal via phosphorylation cascades
include many growth factors - VEGF, EGF, M-CSF, Ephrin, insulin receptors
What is the main role of the insulin receptor?
increase glucose uptake
What other things happen in diabetes?
degradation of receptor
down regulation of pI3K and IRS proteins - downstream signalling components - by high glucose
What are adhesion receptors?
allow spatial patterning, migration, differentiation, guidance, morphogenesis
Examples of adhesion receptors?
Ig superfamiy Cadherin Integrins Selectins Proteoglycans
What are the crucial molecules in the leukocyte adhesion-cascade?
selectins integrins ICAMs JAMs PECAM/CD31
What do selectins do in leukocyte adhesion-cascade?
capture and rolling
bind sugars
signal PIKgamma = slow rolling
What do integrins do in leukocyte adhesion cascade?
mediae leukocyte arrest vi outside-in/inside-out signalling
What is the disease for migration defects in neutrophils?
LAD - Leukocyte Adhesion Deficiency
causes recurrent infection
What are adhesive cell interactions during development?
segregation of tissues
dispersion of cells
cell guidance
cavity formation
What is metastasis?
movement or spreading of cancer cells from one organ/tissue to another via blood/lymph stream
What do microbial receptors/PRR detect?
PAMPs
TLR recognise carbohydrates in cell wall of bacteria
What are defects in microbial recognition?
TLR - cannot recognise fungi if PRR removed
humans - get rid of lectins involved in binding to candida = oral thrush - lectin important for binding to sugars
How do pathogens exploit host receptors?
HIV bind to T cells
receptor allows viral binding and escape into cell
How does listeria exploit phagocytic receptors?
integrins phagocytose and uptake listeria into cell - proteins form pores within vacuole membrane - escape into cytosol
