final cell bio

endosymbiont theory

bacteria got engulfed by a larger prokaryote cell, and couldnt live by itself → became mitochondria

evolution of membrane enclosed organelles

invagination of the plasma membrane

how do ribosomes synthesize proteins

read genetic code by mRNA, tRNA bring specific amino acid to ribosomes to add to peptide

what destinations can cytosolic proteins go to?

mitochondria/chloroplast, nucleus, peroxisomes or cytosol

what destinations can proteins made in the rough ER go?

ER, golgi, plasma membrane or lysosomes

where can import to ER or mito signal sequences be located ?

N-terminus

where can retention in ER signal sequence be located?

C-terminus

where can nucleus (import/export) and peroxisome (import) signal sequences be located?

middle

cellular localization before and after

signal sequences and post translation modifications

what are post translational modifications

lipidation (add fatty acid), phosphorylation (signalling), or ubiquidation (tag to destroy)

how do proteins get into the nucleus (spec)

nuclear import receptor recognizes signal → binds to protein → goes through nuclear pore →ranGTP binds to receptor and dissociates from protein → goes out through nuclear pore → GTP is hydrolyzed and ranGTP dissociates as it picks up a new protein

how do proteins get into the mitochondria

protein unfolds → import receptor protein recognizes and binds to signal sequence → starts feeding it through protein translocator in outer membrane →protein signal sequence is recognized by inner protein translocator and is fed through → translocated fully into matrix → folded up → signal sequence cleaved

how do free ribosomes synthesize proteins

free ribosomes pick up an mRNA and translate directly into cytosol

how do ribosomes synthesize proteins in the rough ER

SRP recognize ER signal sequence → bind to SRP receptor → signal sequence bound to protein translocator and SRP displaced → protein fully translate into ER lumen with signal sequence bound → signal peptidase cleaves signal sequence and leaves in membrane → protein folds up in lumen

how do transmembrane proteins stay in membrane

stop sequence in middle of protein

where do nuclear proteins come from? (cytosol or ER)

cytosol

different protein fates (cytosol/ER)

Cytosol: stay in cytosol, imported into mito/chloro, peroxisome or nucleus

ER: ER→Golgi →plasma membrane or lysosome

Ran-GTP purpose

import into nucleus

GTPgammaS

non-hydrolyzable GTP

necessity

removal to not work

sufficient

addition guarantees event

signal sequences are (necessary/sufficient)

both

proteins synthesized in ER (will/will not) maintain orientation (facing cytosol or facing lumen/outside of cell

will

process of vesicle budding

cargo receptor accepts cargo → adaptin binds to cargo receptor → clathrin binds and starts to bud out →dynamin pinches off vesicle → clathrin and adaptin unbind from vesicle

what does dynamin need to do to bud from membrane

be hydrolyzed - GTPgammaS makes it so dynamin cant constrict

dynamin is a

GTPase

how to dock vesicles

Tethering: tethering protein grabs rab and pulls it close → docking: t-SNARE and v-SNARE intertwines → fusion: vesicle fuses w membrane and delivers protein, v-snare and t-snare stuck on membrane

most proteins are covalently modified in the …

ER

how are proteins covalently modified

disulfide bonds stabilize structure of proteins destined for outside of cell

what is n-linked glycosylation

olgiosaccharides added to asparagine on proteins

how does glycosylation happen?

lipid linked oligosaccharide transferred to asparagine by oligosaccharyl transferase

proteins with KDEL (used) or folded incorrectly will…

remain in the ER

How does a unfolded protein response occur?

if there is too many unfolded proteins

what is an unfolded protein response?

ER sensor protein activates and creates chaperone proteins, ER expands

what happens if UPR is overwhelmed

apoptosis is triggered

how are proteins synthesized in the rough ER directed to locations

signal sequence, oligosaccharide side chain or other feature

what can tags do?

direct to location, exclude materials for certain vesicles or retrieval

golgi structure

enter; cis golgi face →cis cisterna →medial cisterna →trans cisterna →trans golgi network;exit

how can proteins be further modified in the golgi

phosphorylation, lipidation, further modification of N-linked oligosaccharides

what are the two different secretory processes

constitutive and regulated

what is constitutive secretion

unregulated exocytosis

what is regulated secretion

extracellular signal triggers the secretion of proteins

example of regulated secretion

release of insulin from regulated cells when blood sugar is too high

where are N-linked oligosaccharides found?

on the extracellular portion of the protein

types of endocytosis

receptor mediated, phagocytosis or pinocytosis

how does receptor mediated endocytosis work?

LDL binds to LDL receptors on extracellular plasma membrane → forms a clathrin coated vesicle → uncoats → fuse with endosome → delivery of LDL to lysosome →free cholesterol gets released and LDL receptors are returned to plasma membranes via vesicles

where are endocytosed macromolecules sorted?

endosomes

do all endocytosed molecules go to lysosomes?

no, some are recycled directly into the plasma membrane

hydrolytic enzymes are only active under _ conditions

acidic (~5)

how is the pH of the lumen of the lysosome maintained

ATP driven H+ pump

what is autophagy?

digesting old organelles

what are the three pathways to lysosomes?

phagocytosis/pinocytosis, endocytosis and autophagy

what is the definition of phagocytosis

cellular intake of solid material

what is the purpose of phagocytosis

immune response and nutrient reuptake

what is the method of phagocytosis

extension of pseudopodia engulfing particle

cell types of phagocytosis

immune cells

what is the definition of pinocytosis

cellular intake of fluid

what is the purpose of pinocytosis

immune surveillance, nutrient uptake

what is the method of pinocytosis

invagination of cell membrane, forming vesicles

cell types of pinocytosis

almost all cell types

what are the 4 methods of communication

endocrine, paracrine, neuronal, contact dependant

endocrine: signaling molecule, pathway, distance

hormone, bloodstream, long distance

paracrine: signaling molecule, pathway, distance

local mediator, signaling cell, local

neuronal: signaling molecule, pathway, distance

neurotransmitter and electrical impulse, synapse and axon, short and long

contact dependent: signaling molecule, pathway, distance

membrane bound, direct, short

how do cells depend on multiple extracellular signals?

different combination of signals make them do different things

the 4 responses of cells

survive, grow and divide, differentiate, die

how are signals fast?

activation of proteins already in the cell

how are signal slow?

activation of protein synthesis

what does acetlylcholine do to: heart pacemaker cell, salivary gland cell and skeletal muscle cell?

decr rate of firing, secretion and contraction

what does adrenaline/epinephrine do to muscle cells

relaxation of smooth muscle

most signalling molecules are too… to bind to a cell surface receptor

large or hydrophilic

what are the three types of cell surface receptors

ion channel coupled receptor, g protein coupled receptors and enzyme coupled receptors

how do ion channel coupled receptors work?

the signaling molecule opens an ion channel and creates a change in membrane potential

what is cortisol and what does it do

hormone signaling molecule made in the adrenal gland in response to stress or low blood glucose levels. incr blood sugar and suppress immune system

kinase turns.. (on/off)

on

phosphatase turns…(on/off)

off

example of kinase cascade

Ras-MAP

what is the Ras protein?

molecular switch

where do ion channel coupled receptors primarily function?

nerve and muscle cells

acetlylcholine ion channel

opens gate to let Na+ into the cytosol

GPCR structure

single polypeptide, binding pocket deep in the protein and large molecle signals usually have large extracellular domain

three subunits of G-proteins

alpha beta gamma

how are alpha/gamma subunits tethered to the membrane?

by lipids

When g-proteins are inactive

alpha is bound to GDP

when g-proteins are active

Alpha releases GDP and bind GTP and creates a signal, beta/gamma can activate another signal

what is a GTPase

hydrolyze GTP

is the alpha subunit a GTPase?

yes

with acetlycholine in heart pacemaker cells, what complex activates the K+ channel?

beta-gamma

what does a membrane bound enzyme do?

second messengers

example of G-proteins - adenyl cyclase

G-proteins turn on adenyl cyclase to produce cAMP

what does cAMP bind to?

protein kinase A → activates enzyme that breaks down glycogen

how do we stop this signalling cascade (adrenaline →cAMP)

caffiene inhibts the enzyme that turns cAMP into AMP

how do g-proteins also activate PKC

beta/gamma complex activates phospholipase C → breaks apart inositol phospholipid into diacyl glycerol and IP3

diacylglycerol → binds to PKC and activates

IP3 → opens Ca2+ channel from ER lumen → binds to PKC

what does PKC do

phosphorlyate proteins

how does GPCR use dissolved gas as a secondary messenger

acetylchoiine → activated NO synthase + arginine → NO diffuses across membrane → NO binds to guanyl cyclase and GTP turns into cGMP → relaxation of smooth muscle cell and dilates blood vessels

examples of NO

nitroglycerin and viagra

how does cholera bacteria affect GPCR

choleria bacteria multiplies in intestine and produces a toxin → binds to GPCR → modifies alpha subunit of G protein so it is always bound to GTP → incr adenylate cyclase activity → incr cAMP → ion channels always open + water → diarrhea

what are enzyme coupled receptors (RTK)

receptor tyrosine kinase, act as both receptors and enzymes, usually only a single helix, can give off multiple signals at a time

how do RTKs work

dimer signal molecule activate RTK → adaptor protein activates Ras-GEF → activates Ras protein on membrane by binding GTP → onward transmission of signal