Fig. 1.11

Nucleus: structure and function

Nucleolus Nucleoplasm

nuclear envelope

Heterochromatin = too compacted,

transcriptionally inactive

Euchromatin = can be transcriptionally active

Nuclear envelope and lamina

Nuclearpore

N. lamina

cytoplasm

heterochromatin

Nuclear laminaNuclear lamina

Lamins are filamentous proteins in the intermediate filament family

Lamin phosphorylation in prophase disassembles the nuclear lamina & allows for nuc. envel. breakdown

Laminins are extracellular proteins, unrelated

Nuclear pore

• nuclear localization signals (nuclear import signals)

• nuclear export signals

• highly regulated

Mitochondria(on)

outermembrane

innermembrane

DNAmatrix

cristaeribosomes ATP synthase

Inner Membrane and matrix

electrontransportsystem

ADP3-

ATP4-

pyruvate

Krebscycle

NADH

ATPsynthaseFADH2

hi [H+]

Antiporter

P04-2 H+

symporter

Endosymbiotic theory: Mitochondria are similar to prokaryotes

• Own circular, naked DNA

• Own ribosomes - similar to prokaryotic– e.g. sensitive to same inhibitors

• Divide by fission

• Double membrane suggests endocytosis

Lysosomes: membranous organelles filled with digestive enzymes

• Breakdown endocytosed materials– Thru’ phagocytosis or

receptor mediated endocytosis

• Breakdown old organelles (residual body)

• Acidic pH

Phagocytosis vs. Autophagy

Phagocytosis

Autophagy

lysosomes

Membrane trafficking

•RER to cis Golgi

•Modified in Golgi (glycosylation, phosphorylation)

•Sorted at trans Golgi network into

•Lysosomal

•Regulated

•constitutive

Synthesis of secreted and membrane proteins

Ribosomes

Rough endoplasmic reticulum

Rough Endoplasmic reticulum

Signal hypothesis: signal peptide, SRP, SRP-receptor, translocon

SRP = signal recognition particle

Smooth ER, lipid synthesis, detox, Ca2+ sequestration

Golgi

Transport thru’ Golgi cisternae is vectorial

Cis Medial Trans

mannose removalN-acetylglucosamine addition MEDIAL

RER retrieval, PO4 on mannose,mannose removal

CIS &CGN

fucose and glucose addition TRANS

sialic acid addition, sorting TGN

Protein modifications occur in steps in the Golgi. The extent of changes varies.

Glycosylation

Karp, Fig. 8.20

trans Golgi network

regulatedsecretion

lysosomalpathway

constitutivesecretion

Sorting at the TGN

Receptor Mediated endocytosis

Plasma membrane & Fluid mosaic model

Phospholipids are most common in membranes

PolarHead

Fattyacidtails

phospholipids, glycolipids, and cholesterol

Thermodynamics drives membranes to form sealed compartments

H2O

Cut open liposome

Fluidity means that lipids (& proteins) can “float” in the membrane via

diffusion

Time

Three classes of membrane proteins: Transmembrane proteins (a type of IMP)

OUT

IN

Extracellulardomain (ECD)

Intracellulardomain (ICD)

Transmembranedomain

Oligosaccharides - always face out

Three classes of membrane proteins: Lipid-anchored membrane proteins (IMPs)

OUT

IN

Covalently linked to a glycophospholipid.

E.G.: Normal cellular scrapie protein & alkaline phosphatase

Covalently linked to fatty acid

E.G.: ras

Three classes of membrane proteins: Peripheral membrane proteins (PMPs)

OUT

INOr, PMPs could bind to specific lipid heads.

Specific interaction between IMP & PMP

IMPs as -helix or -barrel

Selective permeability

Osmosis causing cell lysis.

Four mechanisms by which solute molecules move ACROSS membranes

Simple diffusionacross bilayer

Simple diffusionthru channel

FacilitatedDiffusion

thru’ passive transporters

Activetransport

Membrane Potential Affects Molecular Movement

A. neutral

No effect on inward transport No effect on outward transport

B. cation

Favors inward transport Opposes outward transport

C. anion

Opposes inward transport Favors outward transport

Passive transport by channel proteins: don’t bind solute & can

be ligand-, voltage-, or stress-gated

Passive Transport by Facilitated diffusion

•Solute binds transporter protein

•So, transport is saturable

Kinetics of carrier-mediated transport

Active transport by the Na/K pump or ATPase