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CELL ORGANELLES AND NUCLEUS
MBBS1
2011
A. Mwakikunga
LEARNING OBJECTIVES
Identify major cell regions - cytoplasm, nucleus
Name any two cellular activities that take place a nucleus
Briefly describe the structural organization of the nucleus and
nuclear envelope
Mention membrane bound organelles
Discuss the roles of intramembrane system of a cell
Describe structural and functional differences among membrane
bound organelles
Discuss the significance of tags, v-SNAREs and t-SNAREs in protein
sorting and targeting
Mention proteins used to coat transport vesicles
Describe briefly how mitochondria are used in the process of
apoptosis
MAIN REGIONS OF THE CELL
Two main regions of a cell are: nucleus
cytoplasm
Cytoplasm + nucleus = Protoplasm
NUCLEUS
One of most prominent & characteristic
features of eukaryotic cells - stores genetic
material
Site where:
chromosomes are localized (heterochromatin vs
euchromatin)
chromosomes are replicated
DNA is transcribed
Surrounded by a bouble-membrane nuclear
envelope
NUCLEAR ENVELOPE
Is composed of inner
& outer nuclear
membranes separated
by perinuclear space
Inner membrane is on
nuclear lamina
Outer membrane is
continuous with ER
NUCLEAR ENVELOPE CONTD…
Nuclear envelope has
nuclear pores
Passage of substances
between cytoplasm &
nucleoplasm
Nuclear pore has many
structural proteins
forming nuclear pore
complex
MACROMOLECULAR TRANSPORT INTO & OUT OF THE NUCLEUS
Proteins needed in
nucleus are
transported inward
from cytoplasm
RNA molecules &
ribosomal subunits for
protein synthesis in
cytoplasm are
transported outward
TRANSPORT MECHANISM OF PROTEINS FROM CYTOPLASM INTO NUCLEUS
NUCLEAR MATRIX, LAMINA & NUCLEOLUS
80-90% of nuclear mass is chromatin fibers
Remaining forms nuclear matrix
supports chromatin fibers
maintains shape of nucleus
Nuclear lamina - lines inner membrane and
supports nuclear envelope
May provide attachment site for chromatin
Nucleolus - condensed component of
eukaryotic nucleus
manufactures ribosomes
CYTOPLASM
Cytoplasm has organelles & inclusions
Organelles (little organs) include membrane systems & membrane bound compartments & nonmembranous structural components
Inclusions - materials that may or may not be surrounded by a membrane
CYTOPLASM
CYTOPLASM CONTD…
Examples of inclusions:
secretory granules, pigments, neutral fats,
glycogen, stored waste products
Cytoplasmic ground substance used to be
called cytosol; now called cytoplasmic
matrix
INTRACELLULAR MEMBRANES OR ENDOMEMBRANE SYSTEM
Most organelles & inclusions are membrane bound
Membranes form vesicular, tubular & structural
patterns that may be convoluted (SER) or plicated
(inner mitochondria)
They provide surface area for chemical reactions
Spaces enclosed by membranes are
microcompartments in which substrates &
products of chemical reactions are segregated or
concentrated
ENDOMEMBRANE SYSTEM
INTRACELLULAR MEMBRANES OR ENDOMEMBRANE SYSTEM CONT..
These membranes are related through
direct physical continuity or by transfer of
membrane segments as vesicles
Thickness, molecular composition &
metabolic behaviour of a membrane are not
fixed; they may be modified during its life
MEMBRANE BOUND ORGANELLES
Cell (plasma) membrane
Rough - endoplasmic reticulum
Smooth - endoplasmic reticulum
Golgi apparatus
Mitochondria
Lysosomes
Endosomes
Peroxisomes
NONMEMBRANOUS ORGANELLES
Microtubules
Filaments
Centrioles
Ribosomes
CELL MEMBRANE
It is a bilayer of phospholipids sandwiched with glycoproteins and cholesterols
On the surface, glycolipids & glycoproteins form a cell coat or glycocalyx
It has a trilaminar appearance in Transmission Electron Microscopy:
Outer electron - dense layer
Inner electron - dense layer
Intermediate nonstaining layer
CELL MEMBRANE
CELL MEMBRANE
CELL MEMBRANE CONTD…
It is a fluid & dynamic system - not a static
structure (modified fluid mosaic model)
It is a mosaic of protein molecules in a fluid
bilayer of phospholipids
Phospholipids are amphipathic - have both
hydrophilic & hydrophobic regions
FLUID QUALITY OF A MEMBRANE
It is not static; weak bonds hold it together
Phospholipids move along its plane at
about 2µm per sec.
Unsaturated hydrocarbon tails have kinks
that keep molecules from packing closely
together, enhancing membrane fluidity
Cholesterol reduces phospholipid
movement
MEMBRANES AS MOSAICS
It has many different proteins embedded in fluid matrix of phospholipids
These are integral & surface proteins
Membrane proteins are for: Transport - ion pumps, channels
Enzymatic activity
Signal transduction
Cell - cell recognition; receptors
Attachment to cytoskeleton & extracellular matrix (adhesion)
MEMBRANES AS MOSAICS
CELL MEMBRANE AS BOUNDARY & BARRIER
Some substances pass it by diffusion, others by active transport
Endo- & Exocytosis - vesicular transport of substances entering & leaving cell respectively
Forms of endocytosis: phagocytosis & pinocytosis
CELL MEMBRANE AS SITE FOR SPECIFIC FUNCTIONS
Organization and localization of function
Compartmentization eg
Mitochondria
lysosomes
Peroxisomes
ER, Golgi complex
ROUGH - ENDOPLASMIC RETICULUM
Endoplasmic - within plasm; reticulum - network
ER coined because it resembled a reticule - netted
hand-bag popular in late 19th century
It is continuous with nuclear envelope
A series of interconnected membrane-bound
flattened sacs called cisternae
rough ER membranes form large flattened sheets
Has ribosomes - protein synthesis
Ergastoplasm - basophilic region of cytoplasm -
represents rER in secretory cells
ROUGH ENDOPLASMIC RETICULUM CONTD…
Groups of ribosomes form polyribosomes
or polysomes attached to mRNA
Polysomes synthesize proteins for export &
integral proteins of cell membrane
Secretory proteins pass through rER
membrane to its lumen for modification &
storage
Free ribosomes synthesize proteins to be
used within the cell
ROUGH - ENDOPLASMIC RETICULUM
ROUGH ENDOPLASMIC RETICULUM CONTD…
rER involved in protein biosynthesis
rER involved in initial protein processing
Initial glycosylation
Polypeptide folding - Alzheimer’s disease
Assembly of multi-subunit proteins
Quality control
Transtional elements - rER subdomain
Form transition vesicles - shuttle lipids &
proteins to Golgi apparatus.
SMOOTH ENDOPLASMIC RETICULUM
Has short tubules not associated with
ribosomes
Cells with a lot of sER show acidophilia or
may appear empty when viewed with light
microscopy
Well developed in cells synthesizing &
secreting steroids - Leydig cells in testis
Found abundantly in liver cells
SMOOTH - ENDOPLASMIC RETICULUM
Detoxifies drugs & other noxious substances
Hydroxylation - addition of hydroxyl groups to
organic acceptor molecules. This increases
solubility of hydrophobic drugs in water.
It is also involved in:
lipid absorption
Glycogen metabolism
Membrane formation & recycling – phospholipids
Calcium storage - in muscles - sarcoplasmic retic.
GOLGI APPARATUS
1898 - described by Camillo Golgi in nerve
cells
System of membranes parallel to each
other
Very active in secretory cells - exocytosis
It doesn’t stain with H & E; exhibits a clear
area surrounded by ergastoplasm as in
osteoblast
GOLGI APPARATUS
Has 2 faces:
forming face or cis-Golgi closest to rER
maturing face or trans-Golgi closest to cell
membrane
Transport vesicles carry newly synthesized
protein from rER to forming face of Golgi A
Coated vesicles - clathrin, COP1, COPII proteins
Condensing vacuoles pinch off from
maturing face & modified into secretory
vacuoles
GOLGI APPARATUS
GOLGI APPARATUS
Acts as a post office for the cell: Packing & shipping
Modifying
Sorting - length of transmembrane domains determine
sorting within Golgi
Recycles proteins (retrograde) & ER-specific protein
retrieval - tags eg KDEL (Lys-Asp-Glu-Leu)
Delivering enzymes to lysosomes
Handles distribution of newly synthesized
membranes & their proteins
Synthesizes polysaccharide & emulsify lipid
GOLGI APPARATUS
SNARE HYPOTHESIS
SNARE for SNAP receptor
This hypothesis connects coated vesicles
& target membranes
The molecular components that facilitate
sorting and targeting of vesicles include 2
families of SNARE proteins: v-SNAREs & t-
SNAREs
these allow a vesicle to recognize a target
organelle
MITOCHONDRIA
Power plants of cells - Krebs Cycle & ETS
Have DNA & RNA; exhibit cell division &
make own structural proteins
Depend on DNA & free ribosomes of cell for
other proteins
Present in all cells except for RBCs &
terminal keratinocytes
Use inner membrane to create functional
compartments
MITOCHONDRIA
Change its structure related to function
2 configuratons in TEM: orthodox &
condensed
Orthodox configuration
cristae prominet, matrix compartment large, low
level of oxidative phosphorylation
Condensed configuration
cristae not easily recognized, matrix
concentrated & reduced, high level of oxidative
phosphorylation
MITOCHONDRIA
MITOCHONDRIA
MITOCHONDRIA
Very crucial in apoptosis - cytoskeletal
disintegration, metabolic derangement,
genomic fragmentation
Intrinsic pathway
p53, Bid, Bak, bax
Cytochrome c
Apaf1 + procaspase 9 → caspase 3 → death
LYSOSOMES
Discovered in 1953 by Chriatian de Duve
Suicide bags with hydrolytic enzymes; single
membrane
Isolate digestive enzymes from the rest of the cell
Develop from late endosomes
Organelles with full complement of acid hydrolases, BUT
not yet engaged in digestive activity
Mature to form fully active lysosomes after acid
hydrolases from TGN are combined with extra &
intracellular material from early endosomes.
LYSOSOMES CONTD…
Primary lysosomes - newly formed
Secondary lysosomes
phagosomes or heterophagic - substance
extracellular origin
autophagic - with materials of intracellular
origin
Tertiary lysosome or residual body - is
debris filled vacuole of broken down
contents of sec. lysosome
IN SUMMARY - ENDOSOMES
Vesicles formed as a result of phagocytosis
They receive lysosomal enzymes from
clathrin-coated transported vesicles
Late endosomes - with inactive enzymes,
mature to form lysosomes
The pathway followed by endosomes within
cell depends on their contents eg It may fuse with lysosome to form phagosome
It may fuse with another domain or region of cell
membrane to release its product from cell (transcytosis)
TARGETTING SOLUBLE LYSOSOMAL PROTEINS TO ENDOSOMES AND LYSOSOMES
It is a model for protein sorting in the TGN
Mannose-6-phosphate is used to target soluble
lysosomal proteins to endosomes and lysosomes
lysosomal enzyme synthesised & carbohydrate added
mannose is phosphorylated
mannose-6-phosphate binds to receptor on the enzyme
tagged enzyme is parked in transport vesicles
During late endosome stage, pH is lowered, enzyme
dissociates from receptor as endosome matures into a
lysosome
PEROXISOMES (MICROBODIES)
0.5µm in diameter; single membrane
Not derived from ER
Therefore NOT part of endomembrane syst
Have oxidative enzymes eg catalase & other peroxidases - break down hydrogen peroxide (H2O2)
H2O2 is toxic
Catalase regulates H2O2 so protecting cell
Numerous in liver and kidney cells
Take part in oxidation of fatty acids