Inner Life of the Cell (Full Version - Narrated)

Full version of inner life of the cell, narrated with music.

While red blood cells are carried away
at high velocity by a strong blood flow,

leukocytes roll slowly
on endothelial cells.

P-selectins on endothelial cells
interact with PSGL-1,

a glycoprotein on leukocyte microvilli.

Leukocytes, pushed by the blood flow,
adhere and roll on endothelial cells

because existing interactions are broken
while new ones are formed.

These interactions are possible

because the extended extracellular
domains of both proteins

emerge from the extracellular matrix, which
covers the surface of both cell types.

The outer leaflet of the lipid bilayer

is enriched in sphingolipids
and phosphatidylcholine.

Sphingolipid-rich rafts raised above
the rest of the leaflet

recruit specific membrane proteins.

Rafts' rigidity is caused by the tight
packing of cholesterol molecules

against the straight sphingolipid's
hydrocarbon chains.

Outside the rafts kinks in
unsaturated hydrocarbon chains

and lower cholesterol concentration
result in increased fluidity.

At sites of inflammation,

secreted chemokines bound to
heparin sulfate proteoglycan

on endothelial cells, are presented to
leukocyte-7 transmembrane receptors.

The binding stimulates leukocytes

and triggers an intracellular cascade
of signaling reactions.

The inner leaflet of the bilayer

has a very different composition
than that of the outer leaf.

While some proteins traverse the membrane,

others are either anchored
into the inner leaflet

by covalently-attached fatty acid chains,

or are recruited through non-covalent
interactions with membrane proteins.

The membrane-bound protein complexes are
critical for the transmission of signals

across the plasma membrane.

Beneath the lipid bilayer, spectrin
tetramers arranged into a hexagonal network

are anchored by membrane proteins.

This network forms the
membrane skeleton that contributes

to membrane stability and
membrane protein distribution.

The cytoskeleton is comprised of networks
of filamentous proteins that are responsible

for the special organization
of cytosolic components.

Inside microvilli, actin filaments
form tight parallel bundles

which are stabilized
by crosslinking proteins.

While vapor in the cytosol, the actin
network adopts a gel-like structure

stabilized by a variety
of actin-binding proteins.

Filaments kept at their minus ends
by a protein complex

grow away from the plasma membrane

by the addition of actin monomers
to their plus end.

The actin network is
a very dynamic structure,

with continuous directional
polymerization and disassembly.

Severing proteins induce
kinks in the filament

and lead to the formation
of short fragments

that rapidly depolymerize
or give rise to new filaments.

The cytoskeleton includes
a network of microtubules

created by the lateral association
of protofilaments,

formed by the polymerization
of tubulin dimers.

While the plus ends of some microtubules
extend toward the plasma membrane,

proteins stabilize the curved conformation
of protofilaments from other microtubules,

causing their rapid
plus-end depolymerization.

Microtubules provide tracks along
which membrane-bound vesicles travel

to and from the plasma membrane.

The directional movement
of these cargo vesicles

is due to a family of motor proteins
linking vesicles and microtubules.

Membrane-bound organelles like mitochondria
are loosely trapped by the cytoskeleton.

Mitochondria change shape continuously,
and their orientation is partly dictated

by their interaction with microtubules.

All the microtubules originate from the
centrosome, a discrete fibrous structure

containing two orthogonal centrioles
and located near the cell nucleus.

Pores in the nuclear envelope
allow the import of particles

containing mRNA and proteins
into the cytosome.

Here, free ribosomes translate the
mRNA molecules into proteins.

Some of these proteins
will reside in the cytosome.

Others will associate with specialized
cytosolic proteins and be imported

into the mitochondria or other organelles.

The synthesis of cell-secreted
and integral membrane proteins

is initiated by free ribosomes,
which then dock to protein translocators

at the surface of the
endoplasmic reticulum.

Nascent proteins pass through an
aqueous pore in the translocator.

Cell-secreted proteins accumulate in
the lumen of the endoplasmic reticulum,

while integral membrane
proteins become embedded

in the endoplasmic reticulum membrane.

Proteins are transported
from the endoplasmic reticulum

to the Golgi apparatus by vesicles
traveling along the microtubules.

Protein glycosylation initiated
in the endoplasmic reticulum

is completed inside the lumen
of the Golgi apparatus.

Fully-glycosylated proteins
are transported

from the Golgi apparatus
to the plasma membrane.

When a vesicle fuses with
the plasma membrane,

proteins contained in the
vesicle's lumen are secreted,

and proteins embedded in the vesicle's
membrane diffuse in the cell membrane.

At sites of inflammation, chemokines
secreted by endothelial cells bind to

the extracellular domains of
G-protein-coupled membrane receptors.

This binding causes a conformational change
in the cytosolic portion of the receptor,

and the consequent activation
of the subunit of the G-protein.

The activation of the G-protein subunit

triggers a cascade of protein
activation which, in turn,

leads to the activation and clustering
of integrins inside lipid rafts.

A dramatic conformational change occurs

at the extracellular domain
of the activated integrins.

This now allows for their interaction with
I-Cam proteins displayed at the surface

of the endothelial cells.

These strong interactions immobilize

the rolling leukocyte at
the site of inflammation.

Additional signaling events cause a
profound reorganization of the cytoskeleton

resulting in the spreading
of one edge of the leukocyte.

The leading edge of the leukocyte
inserts itself between endothelial cells,

and the leukocyte migrates through the
blood vessel wall into the inflamed tissue.

Rolling, activation, adhesion,
and transendothelial migration

are the four steps of a process
called leukocyte extravasation.