Cellular Regulation Flashcards
Cell membrane components(3), and functions(3)
components;
- phospholipids
- cholesterol
- proteins
functions
- protection
- transport
- communication
Cytoskeleton components
- microtubules
- microfilaments
- intermediate filaments
What is the role of microtubules?
- resist compression
- maintain cell shape
- important for motility; form flagella and cilia
Microfilaments;
- resist tension
- form cortical network beneath plasma membrane
- important for movement; actin & myosin interactions for muscle contraction.
Intermediate filaments
- form more permanent structure
- anchor organelles
- important in cell adhesion
- e.g. cytokeratin, neurofilaments, lamins.
Endomembrane system
contains;
- endoplasmic reticulum(smooth & rough)
- golgi apparatus
-vesicles
functions to modify, package, and move proteins & lipids
Protein kinases
- cellular mechanism of ‘activating’ proteins
- selectively modify proteins
- add phosphate to amino acid on protein
- need ATP
Phosphorylation
most common PTM
- addition of phosphate to molecules
- adds negative charge
- causes folded protein to adjust shape
- done by protein kinases and protein phosphatases.
Lipid soluble ligands - examples
- steroids, cholesterol derived
- cortisol(adrenal cortex)
- aldosterone(adrenal cortex)
- progesterone, estradiol & testosterone(gonads)
- neurosteroids(neurons & glial cells)
Aldosterone, role& signalling pathway
- corticosteroid
- part of RASS system
- needed for sodium reabsorption in the nephron
pathway; - binds to mineralocortoid receptor in cell
- receptor-ligand complex translocates to nucleus
- upregulates synthesis of sodium/water absorption - related proteins
Thyroid hormone
- travels in blood bound to carrier
- lipophilic, but iodine charge prevents crossing membrane - enter through channels
- active form T3, common form T4
pathway - thyroid hormone receptor located inside nucleus, bound to DNA response element
- inhibits gene transcription when inactive, activation initiates gene transcription
- involved in metabolism, protein synthesis and bone growth.
GPCR pathways
pathways;
- cAMP –> activates adenylyl cyclase(AC), which converts ATP to cAMP. –> ion channel opening, affecting gene transcription, change molecules.
- Phospholipase C –> converts PIP2 to IP3 and DAG –> IP3 binds to SER for calcium release, DAG activates PKC for phosphorylation.
Cortisol actions, pathway, transport, & receptor
actions;
- suppresses immune system
- increases blood sugar
- increases metabolism
- increases sodium & water retention
- effect on memory
release;
- corticotropin releasing hormone(CRH) released by hypothalamus
- Adrenocorticotropic hormone(ACTH) released by anterior pituitary
- activates GPCR, more intracellular cAMP, PKA stimulation, resulting in upregulation of gene expression for cortisol.
transport & reception
- corticosteroid-binding globulin
- glucocorticoid receptor in cytosol
nicotinic Ach receptor
- ligand gated ion channel
- 5 subunit channel
- located at neuromuscular junctions in brain
- cause Na+ influx
- Na+ influx causes voltage-gated ion channels
JAK-STAT receptor
- cytokine receptor
- bound by growth hormone or prolactin
pathways - ligand binds to receptor monomers
- receptor dimerizes
- JAKs brought closer and cross phosphorylated
- cytoplasmic STATs phosphorylated, dissociate and dimerize
- go to nucleus - gene transcription
Insulin receptor
- receptor tyrosine kinase
- upon binding, dimerizes and cross phosphorylates
2 pathways - PI3K –> GLUT4 channel opens
- Ras pathway –> transcription
CRISPR
- Gene editing tool
- Cas enzyme + guide RNA breaks target sequence, and faultily repair it, causing mutations.
protein-based lab methods
- immunohistochemistry
- western blot
- co-immunoprecipitation
- mass spectrometry
RNA-based lab methods
- quantitative PCR
- RNA sequencing
Live cell methods
- calcium imaging
- electrophysiology
sAPPa
a signalling molecule
- protects neurons from damage
- promotes neuronal growth and plasticity
IHC
uses antibodies to visualise antigens
- primary antibody binds to antigen of interest
- secondary antibody binds to primary antibody
- enzyme complex added to amplify signal, and interact with dye
- either a dye or fluorescing agent.
Autocrine
Communication between nearby cells of the same type
- signal molecule release and recepted
- specificity by selective receptor expression and rapid degradation
Juxtacrine
communication by cell-cell contact
- often has gap junctions
- rapid
Paracrine
local signalling between difference cell types
Endocrine
signaling between distant cells
- utilizes vascular system
cAMP signalling pathway
Gs alpha subunit binds to a adenylyl cyclase activating it
- adenylyl cyclase converts ATP to cAMP
–> open nucleotide gated channels
–> activate EPAC
–> activate PKA
PKA
–> glygogen to glucose
–> gene transcription
–> faster heart muscle contraction
PLC pathway
gq alpha subunit activates phospholipase C at plasma membrane
PIP2–> IP3 & DAG
- IP3 causes SER calcium release
- DAG activates PKC
Adrenaline
- signals through GPCR
- alpha subunit trades GDP for GTP, activates adenylyl cyclase
–> more cAMP = increase PKA function
–> PKA increases activity of glycogen phosphorylase, and decreases activity of glycogen synthase.
apoptosis
- programmed cell death
- fas ligand binds to Fas (TNF) receptor –> receptor trimerises –> bind FADD –> forms DISC –> activates caspases
Stroke and glutamate excitotoxicity
Ishaemic stroke - too litle oxygen.
- glulamate release,
- decreased glutamate uptake
- leads to cytotoxicity
COVID-19
binds ACE2 receptor–> regulates angiotensin II –> increases blood pressure and inflammation
Asthma inhalers
agonist for B2 adrenergic receptor agonist –> airway relaxation & reduced inflammation
Selective serotonin reuptake inhibitors
- mood-controlling neurotransmitter
- ssri’s prevent uptake; more lasting serotinin
Immodium
- treats diahorrea –> slows gut peristalsis
Paracetamol
inhibits enzymes COX 1&2 that produce prostaglandins, prevent inflamation.
- antagonist of TRPV1 receptor
