Intracellular Compartments and Protein Sorting

Haixu Tang

School of Informatics

The major intracellular compartments of an animal cell

Relative Volumes Occupied by the Major Intracellular Compartments

INTRACELLULAR COMPARTMENT PERCENTAGE OF TOTAL CELL VOLUME

Cytosol 54

Mitochondria 22

Rough ER cisternae 9

Smooth ER cisternae plus Golgi cisternae

6

Nucleus 6

Peroxisomes 1

Lysosomes 1

Endosomes 1

An electron micrograph

Development of plastids

Hypothetical schemes for the

evolutionary origins of some organelles

Four distinct families

1) the nucleus and the cytosol, which communicate through nuclear pore complexes and are thus topologically continuous (although functionally distinct);

2) all organelles that function in the secretory and endocytic pathways, including the ER, Golgi apparatus, endosomes, lysosomes, the numerous classes of transport intermediates such as transport vesicles, and possibly peroxisomes;

3) the mitochondria;

4) the plastids (in plants only).

Secretory vs. endocytic pathways

Protein traffic

Protein traffic

• Gated transport

• Transmembrane transport

• Vesicular transport– membrane-enclosed transport

intermediates

Sorting sequences

Some sorting sequences

Prediction of protein sorting

• Psort web server: http://psort.nibb.ac.jp/– prediction of protein localization sites in cells

from their primary amino acid sequence

Construction of Membrane-enclosed Organelles Require Information in the Organelle Itself

• The information required to construct a membrane-enclosed organelle does not reside exclusively in the DNA that specifies the organelle's proteins. Epigenetic information in the form of at least one distinct protein that preexists in the organelle membrane is also required, and this information is passed from parent cell to progeny cell in the form of the organelle itself. Presumably, such information is essential for the propagation of the cell's compartmental organization, just as the information in DNA is essential for the propagation of the cell's nucleotide and amino acid sequences.

Nuclear pore complexes

Nuclear Envelope

Nuclear lamina

• Consists of "intermediate filaments", 30-100 nm thick.

• These intermediate filaments are polymers of lamin, ranging from 60-75 kD.

• A-type lamins are inside, next to nucleoplasm; B-type lamins are near the nuclear membrane (inner). They may bind to integral proteins inside that membrane.

• The lamins may be involved in the functional organization of the nucleus.

Nuclear localization signals (NLSs)

Protein import through nuclear pores

Possible paths for free diffusion through

the nuclear pore complex

Nuclear Import / Export Receptors

The control of nuclear import during T-cell activation

The breakdown and re-formation of the nuclear envelope during mitosis

The subcompartments of mitochondria and chloroplasts

A signal sequence for mitochondrial protein import

Protein translocators in the mitochondrial membra

Protein translocation depends on the temperature

Protein import by mitochondria

Energy required

Two plausible models of how mitochondrial hsp70 could drive protein import

Protein import from the cytosol into the inner mitochondrial membrane or

intermembrane space

Translocation of a precursor

protein into the thylakoid

space of

chloroplasts

The Endoplasmic Reticulum

Free and membrane-bound ribosomes

The signal hypothesis

The signal-recognition particle (SRP)

SRP direct ribosomes to the ER membrane

Protein translocation

Single-pass transmembrane protein

Multipass membrane protein rhodopsin

Protein glycosylation in the rough ER

The export and degradation of misfolded ER proteins

The unfolded protein response in yeast

Phospholipid exchange proteins