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Lecture

Important Terms and Definitions

3 Pages
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Department
Biological Sciences
Course Code
BIOB10H3
Professor
Aarti Ashok

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LECTURE#4
x ^}µ_ZÀ]oµZZÀ}}(}o}]v
x KW//À]oWv}}]v^(}Á(}u ER to Golgi t anterograde transport
x KW/À]oWv}}]v^_(}u'}oP]}ZvÁ]Z]vZ'}oP](}ud'E}
cis-Golgi t retrograde transport
x Two types of proteins are involved in targeting vesicles to specific compartments:
o Rab proteins t direct vesicles
o SNAREs taid in docking and fusion of vesicles
x COP II vesicles
x ERGIC = ER-Golgi intermediate compartment
x CGN = cis- Golgi network, proteins are sorted to determine which ones need to be brough back
to the ER vs. ones that will move on through the Golgi through signals
x TGN = trans-Golgi network; sorts proteins that are headed to the plasma membrane or to
various intracellular organelles through signals for specific destination f proteins; eg. lysosomal
proteins would bear different signals
x Proteins moving through the Golgi:
o Vesicular Transport Model t Anterograde movement: move non-resident proteins
forward tproteins move, stacks remain in place
o Cisternal maturation model tRetrograde movement: resident proteins are retrieved
back from the stacks
x Glysosylation in the Golgi:
o N-linked glycoproteins: sugars are trimmed and other sugars are added is referred to as
complex N-linked glycosylation- reqd for proteins to achieve final functional state and is
done by glycotransferases present in sequential stacks; assembly line
o O-linked glycosylation: sugars are attached to serine or threonine on specific proteinsv
happens specifically in the golgi; proteins are already folded before this type of glycan
addition; based on the shape/conformation of specific serine and threonine
x COPII Proteins; ER to Golgi t vesicles carry proteins from the site of synthesis to cis-Golgi (via
ERGIC)
x Secretion is the default pathway for proteins t can be constitutive or regulated by a signal;
proteins required elsewhere are sorted in the cell by using signals on proteins recoqnized by
sorting factors tsimilar to the recognition/sorting by SRP
Protein sorting:
o Soluble ER resident proteins: ER resident proteins bearing the KDEL sequence move from
the ER to Golgi in COP II coated vesicles; the KDEL containing soluble proteins bind the KDEL
receptor which contains a KKXX motif and can bind to the COP I coated vesicles and are thus
moved back to the ER
o COP I vesicles used for retrieval back to the ER; COP II vesicles used to move onwards to TGN
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Description
LECTURE#4 x ^}µ_ZÀ]oµZZÀ}}(}oµo}]v x KW//À]oWv}}]v^(}Á(}u ER to Golgi t anterograde transport x KW/À]oWv}}]v^lÁ_(}u'}oP]}ZvÁ]Z]vZ'}oP](}ud'E}cis-Golgi t retrograde transport x Two types of proteins are involved in targeting vesicles to specific compartments: o Rab proteins t direct vesicles o SNAREs taid in docking and fusion of vesicles x COP II vesicles x ERGIC = ER-Golgi intermediate compartment x CGN = cis- Golgi network, proteins are sorted to determine which ones need to be brough back to the ER vs. ones that will move on through the Golgi through signals x TGN = trans-Golgi network; sorts proteins that are headed to the plasma membrane or to various intracellular organelles through signals for specific destination f proteins; eg. lysosomal proteins would bear different signals x Proteins moving through the Golgi: o Vesicular Transport Model t Anterograde movement: move non-resident proteins forward tproteins move, stacks remain in place o Cisternal maturation model tRetrograde movement: resident proteins are retrieved back from the stacks x Glysosylation in the Golgi: o N-linked glycoproteins: sugars are trimmed and other sugars are added is referred to as complex N-linked glycosylation- reqd for proteins to achieve final functional state and is done by glycotransferases present in sequential stacks; assembly line o O-linked glycosylation: sugars are attached to serine or threonine on specific proteinsvhappens specifically in the golgi; proteins are already folded before this type of glycan addition; based on the shape/conformation of specific serine and threonine x COPII Proteins; ER to Golgi t vesicles carry proteins from the site of synthesis to cis-Golgi (via ERGIC) x Secretion is the default pathway for proteins t can be constitutive or regulated by a signal; proteins required elsewhere are sorted in the cell by using signals on proteins recoqnized by sorting factors tsimilar to the recognition/sorting by SRP Protein sorting: o Soluble ER resident proteins: ER resident proteins bearing the KDEL sequence move from the ER to Golgi in COP II coated vesicles; the KDEL containing soluble proteins bind the KDEL receptor which contains a KKXX motif and can bind to the COP I coated vesicles and are thus moved back to the ER o COP I vesicles used for retrieval back to the ER; COP II vesicles used to move onwards to TGN www.notesolution.com x Lysosomes have a low pH ttypically around 4.6; they havea range of sizes from 45 nm to 1 micrometer x Autophagosomes : eating 1 cell tthe organelle is first surrounded by a double membrane derived from the ER cistern; outer membrane is fused together with the lysosome and the lysosome then digests the organelles tprovides energy to the cell x The beneficial breakdown products are transported to the cytosol and used by the cell as energy x The undigested or unwanted breakdown products can: o Remain in the lysosome, are called residua l bodies; later become lipofuscin granules o Be removed from the cell by exocytosis tlysosomes fusing together with the plasma membrane x Lysosomes are involved in digestion; one specialized function is that they digest macromolecules that make up the extracellular matrix in the cell exterior; delivered by way of endosomes using receptor-mediated endocytosis x Osteolasts: lysosomal contents are released to the cell exterior in cells that degrade bone; leave Z]v]o}(Zv[}v x Protein traffic from the TGN o Constitutive secretion = lysosomal enzymes are transported instead through the Golgi to the cell exterior o Regulated secretion o Move to lysosome and vacuoles x Acid hydrolases that are the lysosomal enzymes are brought to the lysosome by: first synthesized in the ER, glycolsylated in the ER where the N-linked glycan is added, transported to the Golgi in COP II vesicles, specific mannose sugars of the N-linked glycans on the proteins destined for the lysosome are phosphorylated by enzymes in the cis-Golgi x Mannose phosphorylation = signal for transport to lysosome (on N-glycans) ; N-terminal signal sequence needed to make proteins in ER x Mannose phosphorylated lysosomal proteins are recognized in the Golgi by mannose 6-phosphate receptors t MPRs = transmembrane proteins that reside in the TGN x MPRs bounded to proteins with mannose-6-phosphate signal then bud into specific coated vesicles known as clathrin coated vesicles which fuse with endosomes; the endosomes mature into lysosomes containing acid hydrolases x Vacuoles are similar to to lysosomes in that they have proton pumps that keep them acidic x G-proteins- GTP binding protein; needed for budding vesicle to occur x Proteins are first synthesized in the cytosol on free ribosomes for those that need to be sorted into peroxisomes, mitochondria and chloroplasts; import to these organelles occurs post-translationally tdifferent from ER, which imports proteins co-translationally ; all are based on signals x Peroxisomes have a dense core of enzymes involved in many processes t the main one being oxidation x Proton pumps are also classified as lysosomal proteins as well as acid hydrolases x Receptor-mediated endocytosis(RME) t works in 11 easy steps: www.notesolution.com o Cell surface receptors bind the extracellular ligands eg. growth factor, hormones etc. o Clathrin binds to the other end of the receptor on the cytosolic side o Clathrin-coated pits are fromed and bud inwards from the PM o Pits containing the receptor-ligand complexes invaginate into the cytosol and pinch free of membrane forming clathrin-coated vesicles o Clathrin uncoats from vesicles once internalized o Vesicles form early endosome (EE) o The EE matures into a sorting compartment; by way of the lumen acidifying through proton pumps, causing the ligand and receptor to be dissociated o Receptors recycle back to the surface in vesicles o v}}uo]À]o~s[oÀZ}]vP}uuvv(µÁ]ZZoendosome(LE) o >[uµ]v}oÇ}}u o Endocytosed material is broken down by acid hydrolases in lysosomes www.notesolution.comLECTURE#4 N ^ }Z_ZZ] oZZZ }}Z}oo}]LZ N K9Z] oZ9LZ}}]LZ^}}K ER to Golgi J anterograde transport N K9Z] oZ9LZ}}]LZ^ lZ_}K}o2]}ZL]Z]LZ}o2]}[email protected]} cis-Golgi J retrograde transport N Two types of proteins are involved in targeting vesicles to specific compartments: o Rab proteins J direct vesicles o SNAREs Jaid in docking and fusion of vesicles N COP II vesicles N ERGIC = ER-Golgi intermediate compartment N CGN = cis- Golgi network, proteins are sorted to determine which ones need to be brough back to the ER vs. ones that will move on through the Golgi through signals N TGN = trans-Golgi network; sorts proteins that are headed to the plasma membrane or to various intracellular organelles through signals for specific destination f proteins; eg. lysosomal proteins would bear different signals N Proteins moving through the Golgi: o Vesicular Transport Model J Anterograde movement: move non-resident proteins forward Jproteins move, stacks remain in place o Cisternal maturation model JRetrograde movement: resident proteins are retrieved back from the stacks N Glysosylation in the Golgi: o N-linked glycoproteins: sugars are trimmed
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