Cell Flashcards
Name the 5 different ways cells can signal.
Intra-,Auto-, Juxta-, Para-, Endo-crine
Name the 3 categories of cell junctions.
Communicating, occluding, anchoring
Name the 6 types of junctions
Gap, Tight, Adherens, desmosome, Focal adhesion, Hemidesmosome
Gap junction proteins and their functions are :
Connexinx, transport cAMP, Ca and other smaller then a 1000 dalton molecules.
Tight junction protiens and their function
Occludin, claudin, form cell cell junctions by binding actin.separate epidermal layers from ECM and decide spacial polarity’of the cell
Adherens junctions protein and their functions
Cadherin that binds to actin and forms cell-cell junctions
Desmosomes protein and function
Cadherin that binds intermediate filaments and create cell-cell junctions
Focal adhesion protein and function
Integrin that binds actin in cell and fibronectin in ECM to form Cell -matrix junction
Hemidesmosomes, protein and function
Integrin protein that forms cell-matrix junction by binding keratin in cells and laminin in ECM
What are the two main classes of hormones give examples
Peptide and amino acid derived hormones (dopamine, NE,Insulin, IGF1, GH ) and Steroid hormones (Testosterone, progesterone, cortisol, aldosterone)
What is the main difference between. Steroid and Peptide derived hormones?
Peptide hormones need cell surface receptors to mediate their actions (RTKs or GPCRs) while steroid hormones can pass plasma membrane and act on cytosolic or nuclear receptors.
Name 3 gasotransmitters and their effects
NO(vasodilator by smooth muscle relaxation, inhibitor of platelet adhesion), CO(vasodilator by smooth muscle relaxation, anti-inflammatory, anti-proliferative, anti-apoptotic), H2S
Explain constitutive secretion
Vesicles constantly undergoing exocytosis (for proteins without a destination)
Name all the routes of protein secretion
Constitutive, Regulated, Transcytosis, Multivesicular transport, Microvesicles,
Shedding
Explain regulated secretion
Loaded vesicles are stored in cytosol until release signal is received
Explain secretory lysosomes
Capturing proteins and secreting them
Explain multivesicular transport
One large multivesicular body contains exosomes and release them
Explain microvesicles
Vesicles that are not from the Golgi
Explain shedding
ICD of transmembrane protein gets cleaved thus release of ECD of the protein
What is anterogade and retrogade transport? Name coating proteins involved
Anterogade : ER to cis-Golgi (COPII). Retrogade : cis-Golgi-ER (COPI)
What is the function of Clatherin?
Transports cesicles from plasma membrane to the Golgi and the from Golgi to the lysosome
Name the 3 steps and the a short description to each in cesicle formation
Cargo selection (coat and adaptor proteins accumulate, filtration by receptor), Vesicle budding( fission, GTP dependent, uncoating), Vesicle targeting and fusion (Rab-GTP)
Name the receptor and downstream effects of NO and CO
Guanyl cyclase receptor —> cGMP—> vasodilation
Explain the pathway for NO synthesis
Ach binds receptor on endothelial cell —> IP3–> Ca—> Triggers NOS
What do PKRs do?
Cytosolic proteins that dimerize and, bind to viral dsRNA and phosphorylate elF2alpha
to halt translation
Why mRNAs do not bind PKRs?
Because they are sigle stranded and too long
Name the steps of miRNA formation.
Transcription —> pri-miRNA—>Drosha4 &Pasha/DGCR8—>pre-miRNA—>Dicer—> ds-miRNA no loop—>RISC & Ago—> ss-miRNA binds to UTR on mRNA and Ago breaks down mRNA.
Function of siRNAs
In nucleus bind to promoter region. In cytoplasm perfect binding to mRNA promotes its cleavage.
Name the steps of Ras pathway
RTK-Ras-Raf-Mek-Urk
Name general MAPK pathway downstream to RTK
MAPKKK—>MAPKK—>MAPK—>effect
What are scaffold proteins used for in cell signalling?
To hold downstream proteins and signalling molecules close to one another, also in proper order.
What type of receptors can activate PI3K pathway?
RTKs and GPCRs
What does PI3K act on?
converts PIP2 to PIP3 with the help of PTEN
Name 2 downstream effects of PI3K
Ras and AKT
Name two downstream targets of PIP3
PDK1 and AKT
Name a common downstream target of GPCRs and RTKs
Phospholipase C (PLC)
What two compounds are needed for the activation of PKC
Diacylglycerol and Ca
Name the 3 main classes of Nuclear receptors
Steriod receptors, Adopted Orphan receptors, Orphan receptors,
Name the subgroups of Orphan receptors
Monomeric and homodimeric
How many classifications of nuclear receptors exist(NR)?
NR 0-6
What do A & B domains of nuclear receptors contain? What is the function? Where is this domain located?
First two transactivation domain, AF-1, N-terminal
What does C domain of NRs contains?
DBD consisting of two zinc finger DNA binding motifs
What does D domain of NRs consist of?
Hinge region, Nuclear localization sequence (NLS)
What does E domain of NRs contain? Wheere is it located?
Ligand-binding domain(LBD) and second transactivation domain AF-2, located at c-terminal
Sumarize the key feature of nuclear receptors
Ability to regulate different sets of genes within different cell types based on the tissue specific transcriptional complexes
To what NRs can thank their key features
NRs function as inducible scaffolds capable of coordinating large transcriptional complexes
Name general ligands of AhR
Xenobiotics, Flavonoids, Molecules formed by endogenous metabolism
What is inactive cytosolic AhR bound to?
HSP90, p23 and XAP -molecule 2
Explain main steps of the genomic activation pathway of AhR.
Heterodimer formation with ARNT—> BInding to Xenobiotic responsive elements (XRE)
Name the steps of nongenomic AhR activation.
AhR active —> Increased Ca—> activates PKC—>phosphorylation of serine residue on Src—>ahesion disturbance, inflammation, MAPKs
What is the function of Cytochrome P450 genes
Detoxification of lipophilic and nonpolar substances
Chemicals that are able to interact with hormone producing organs or act as a hormones are called :
Endocrine disruptors (EDCs)
What are dioxins?
Polyhalogenated aromatic hydrocarbons
Name the steps of xenobiotic detoxification
Functionalization (addition of oxygen), Conjugation(adding water soluable group), Secretion(into urine or bile)
Name the type of water soluble groups that can be added during Conjugation step
Glucoronic acid, Amino acid, Acetyl group, Methyl group
What is a common intermediate product in detoxification process? Why this compound can be a problem?
Benzo(a)pyrene that can diffuse to the nucleus and cause DNA damage
what are the domains of mTOR?
Heat repeats,FAT domain, FRB domain, Kinase domain, FATC domain
In general what is positevely regulated by mTOR?
Anabolic processes, transcriptio, translation, ribosome biogenesis, nutrient transport and mitochondrial metabolism
In general what are negatively regulated processes by mTOR?
Catabolic processes like mRNA degradation, ubiquitin dependent proteolysis, autophagy and apoptosis
Name pathways that activate the mTORC1
Wnt(TSC2 inhibition), IGF1 and GFs via AKT mediated inhibition of TSC2, Ras via Erk that inhibits TSC2
Name a pathway that inhibits mTORC1
TNF-alpha that inhibits TSC1
What amino acids induce mTORC1 by activating GATOR2? What upstream signal they interfere with?
Leucin inhibits Sestrin2 and Arginine inhibits CASTOR1, both of those inhibit GATOR2
What hypoxia, DNA-damage and glucose deprivation can lead to with regard to mTORC1
All lead to TSC2 activation and thus mTORC1 inhibition
What is the main downstream effector of mTORC1
P70S6 kinase(S6K1)
Give the Fenton reaction below
Fe(II) + H2O2 —> Fe(II) = OH(-) + °OH
Downstream general effects of S6K1
Cap dependent translocation, enhanced translation efficacy, cholesterol and fatty acid synthesis, autophagy supression, oxidative pentose pathway enhance,
Name exact downstream targets of S6K1
elF4B(elF4A release), SKAR(translation eficacy) Lipin (SREBP inhibitor) inhibition, ATF-4 (ribosome biogenesis), ULK1 activation (autophagy supression), TFEB inhibition (UPS turn off)
How does mTORC2 effect IGF1 signaling?
Negatively, its a negative feedback loop
What downstream phosphorylative activation effects does mTORC2 has?
PKA, PKC, PKG and AKT
How does mTORC1 and S6K1 play a role in type 2 diabetes
Prolonged mTORC1 activation —> active S6K1 —> inactive IRS1—> no glucose transporters —> high blood sugar and hypertension
Recite Shh pathway
Shh-Patched-Smoothened-Gli to GliAct activation and Gli to GliRep inhibition. GliAct transcribes Shh target genes