Fundamentals of Biological Sciences
Lecture4
Dr. Açelya Yılmazer
MEMBRANE-ENCLOSED ORGANELLES
• Eukaryotic Cells Contain a Basic Set of Membrane-enclosed Organelles
MEMBRANE-ENCLOSED ORGANELLES
• Eukaryotic Cells Contain a Basic Set of Membrane-enclosed Organelles
• Most of the organelles are held in their relative locations in the cell by attachment to the
cytoskeleton.
– Cytoskeletal filaments providfe tracks for moving the organelles around and for
directing the traffic of vesicles.
– Needs the energy of ATP
• Organelles occupy nearly half of the volume of a eukaryotic cell
• Endomembrane system: ER, Golgi
appraratus, peroxisomes, endosomes and lysosomes
MEMBRANE-ENCLOSED ORGANELLES
• Eukaryotic Cells Contain a Basic Set of Membrane- enclosed Organelles
• Most of the organelles are held in their relative
locations in the cell by attachment to the cytoskeleton.
– Cytoskeletal filaments providfe tracks for moving the organelles around and for directing the traffic of
vesicles.
– Needs the energy of ATP
• Organelles occupy nearly half of the volume of a eukaryotic cell
• Endomembrane system: ER, Golgi appraratus, peroxisomes, endosomes and lysosomes
• Membrane-enclosed Organelles Evolved in Different Ways
PROTEIN SORTING
• Proteins Are Transported into Organelles by Three Mechanisms
PROTEIN SORTING
• Proteins Are Transported into Organelles by Three Mechanisms
• Signal Sequences Direct Proteins to the Correct Compartment
• They are typically 15-60 aa long
• Ex: Proteins destined for the ER possess an N-terminal signal sequence that directs them to that organelle,
whereas those destined to remain in the cytosol lack any such signal sequence.
• Recombinant DNA techniques can be used to change the destination of the two proteins: if the signal sequence is removed from an ER protein and attached to a cytosolic protein, both proteins are reassigned to the expected, inappropriate location.
PROTEIN SORTING
• Proteins Enter the Nucleus Through Nuclear Pores
– Nuclear envelope: encloses the DNA and defines nuclear compartment, formed by two concentric membranes
– Inner nuclear membrane:contains some proteins for chromosome binding
– Nuclear lamina:finely woven meshwork pf
protein filaments that lines the inner surface and provides structural support for the envelope
– Outer nuclear membrane:its composition
resembles ER membrane, and it is continuation of ER membrane
– Nuclear pores:gates on nuclear envelope
through which molecules enter or leave nucleus.
PROTEIN SORTING
• Proteins Enter the Endoplasmic Reticulum While Being Synthesized
– ER serves as an entry point fpr proteins
destined for other organelles, as well as for the ER itself.
• Soluble Proteins Made on the ER Are Released into the ER Lumen
• Start and Stop Signals Determine the
Arrangement of a Transmembrane Protein in the Lipid Bilayer
Movie: ER Tubules
PROTEIN SORTING
• Proteins Enter the Endoplasmic Reticulum While Being Synthesized
– ER serves as an entry point fpr proteins
destined for other organelles, as well as for the ER itself.
• Soluble Proteins Made on the ER Are Released into the ER Lumen
• In the ER lumen, proteins fold up, assemble with their protein partners
• Exit from ER is an important quality control step:
– Proteins fail to fold properly are retained in ER- chaperone proteins
Movie: Protein Translocation
VESICULAR TRANSPORT
• Transport Vesicles Carry Soluble Proteins and Membrane Between Compartments
– Secretory pathway: starts with the synthesis of proteins on ER membrane, their entry to ER, then to Golgi and finally to cell surface
– Endocytic pathway: responsible for
ingestion and degradeation of extracellular molecules (from plasma membrane
through endosomes to lysosomes)
VESICULAR TRANSPORT
• Vesicle Budding Is Driven by the Assembly of a Protein Coat (these vesicles are called
coated vesicles)
• Clathrin: one of the best studied coat
• Clathrin-coated vesicles: bud from Golgi (on secretory pathway) and plasma
membrane (for endocytic pathway)
• At the plasma membrane, vesicle starts as coated pit.
Movie: Clathrin
VESICULAR TRANSPORT
• After a transport vesicle buds from a
membrane, it must find its way to its correct destinatiom to deliver its contents.
• Vesciles are transported by motor proteins that move along the cytoskeleton.
• Once the vescile has reached to its target, it must recognize and dock with a specific
organelle.
• Vesicle Docking Depends on Tethers and SNAREs
• Tether: example Rab proteins
• SNARE: example v-SNARE or t-SNARE
SECRETORY PATHWAYS
• Most Proteins Are Covalently Modified in the ER
– Disulfide bonds (between two cysteine residues, to stabilize protein structure) – Glycosylation (protect proteins from
degradation, guide to the appropriate organelle)
• Exit from the ER Is Controlled to Ensure Protein Quality
– Misfolded proteins are retained in the ER (chaperone proteins for refolding, if failed sent to cytosol for degradation)
SECRETORY PATHWAYS
• Proteins Are Further Modified and Sorted in the Golgi Apparatus
• Golgi apparatus: located near the cell nucleus, close to centrosome.
• Golgi consists of flattened membrane enclosed sacs called cisternae.
• Golgi stack has two faces:
– Cis: entry, adjacent to ER
– Trans: exit, facing plasma membrane
– Proteins enter the cis Golgi network from ER
– Proteins exit from the trans Golgi network – Proteins travel in vesicles by budding from
one cisternae to other
Movie:
SECRETORY PATHWAYS
• Secretory Proteins Are Released from the Cell by Exocytosis
– Vesicles bud from trans Golgi network and fuses with plasma membrane
• Constitutive exocytosis vs regulated exocytosis
1. Supplies plasma membrane with newly sythesized lipids and proteins, enabling the plasma membrane to expand prior to division and
refreshing old lipids and proteins in nonproliferating cells.
2. Carry soluble proteins to outside (secretion)
3. No signal is needed
1. Operates only in
specialized secretory cells. (for hormone, mucus or digestive enxyme secretion 2. Extracellular signal is
needed
ENDOCYTIC PATHWAYS
• Endocytosis: eukaryotic cells are continually taking up fluid, large and small molecules
• Starts with endocytic vesicle (the material to be ingested is enclosed by a small portion of plasma
membrane, which buds inward and forms this vesicle)
• The ingested material within the vesicle are delivered to endosomes then end up in lysosomes for
degradation.
• Two types of endocytosis: phagocytosis and pinocytosis
• Specialized Phagocytic Cells Ingest Large Particles
• Fluid and Macromolecules Are Taken Up by Pinocytosis
ENDOCYTIC PATHWAYS
• Receptor-mediated Endocytosis Provides a Specific Route into Animal Cells
– Example: Low density lipoprotein (LDL) entry to cells
– LDL: cholestrol is transpoted in the blood bound to a protein in the form of LDL.
– LDL: secreted from liver
– Defective gene encoding the LDL receptor:
predisposes individuals to artherosclerosis (due to the accumulation of cholestrol in blood).