Eukaryotic Protein Targeting

Targeting in eukaryotes is necessarily more complex due to the multitude of internal compartments:

nucleus
mitochondria
peroxisomes
chloroplasts
endoplasmic reticulum (ER)
Golgi
lysosomes
secretory granule
etc...

The signals involved are also called sorting signals. They are regions on the targeted protein with certain amino acid sequences.

These signals interact with specific receptors, either on the target organelle or a carrier protein.

There are two basic forms of targeting pathways:

post-translational targeting:

nucleus
mitochondria
chloroplasts
peroxisomes

co-translational targeting (secretory pathway):

ER
Golgi
lysosomes
plasma membrane
secreted proteins

In the absence of targeting signals, a protein will remain in the cytoplasm:

translational machinery
metabolic enzymes
cytoskeletal proteins
many signal transduction proteins

Nuclear targeting:

Unusual since 2-way traffic:

in: proteins, DNA

DNA & RNA polymerases
transcriptions factors
histones etc.

out: mRNA, tRNA, rRNA

Proteins are not transported through the nuclear membrane but rather through a complex pore called the nuclear pore:

comprised of about 100 different proteins
proteins smaller than 20 kDa move by diffusion
proteins larger than 20 kDa move by selective transport (nuclear localization signal/sequence [NLS])

cluster of 4-8 positively charged amino acids (example: PKKKRLV)
signal sequence binds to receptor on the pore called importin

Mitochondrial targeting:

Post-translational targeting, including chaperones and TIM/TOM machinery

Lysosomal targeting:

Lysosomes are organelles that store enzymes which rapidly degrade other proteins and nucleic acids.
Initial targeting via secretory pathway
An ER retention target sequence is "KDEL" for retrograde transport
Final targeting occurs in the Golgi
GoA lysozomal targeting signal is mannose-6-phosphate

Next: The Secretory Pathway

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