email: a.baker@leeds.ac.uk
Research
The development and function of eukaryotic cells requires the accurate delivery
of proteins to subcellular organelles. The consequence to the organism when
these systems malfunction can be catastrophic. Our principal interest is in
the biogenesis of peroxisomes and the targeting and import of peroxisomal proteins.
In humans the failure of these mechanisms results in a debilitating and eventually
fatal group of diseases, the peroxisome biogenesis disorders. In plants they
are likely to have far ranging effects on seed viability, seedling vigour and
the ability to withstand stress; all agronomically important traits. Our goal
is to understand the molecular mechanism by which proteins enter peroxisomes
and to understand how peroxisome biogenesis is regulated to meet the needs
of the organism. We adopt a cross-disciplinary approach studying yeast, plant
and mammalian cells as appropriate. We study the import of peroxisomal proteins
and probe the interaction of translocation intermediates with the import machinery
using an in vitro uptake system derived from sunflower cotyledons. This is
complemented by in vivo targeting studies in yeast and plant cells. Expression
of peroxisome biogenesis genes in plant and mammalian cells is studied using
northerns and RT-PCR as well as promoter-luciferase gene fusions in transgenic
plants. A new area of research is the isolation and characterisation of peroxisome
mutants in the model plant Arabidopsis thaliana.
Schematic diagram of protein
import into peroxisomes
Most peroxisome matrix proteins possess one of two targeting
signals, a C-terminal tripeptide called PTS1 or an N terminal
nonapeptide termed PTS2. These proteins interact with the
cytosolic receptors PEX5 and PEX7 respectively. In mammals
and plants the two pathways are coupled, as an isoform
of PEX5 (PEX5L) is required as an accessory protein for
PEX7. In bakers yeast the two pathways are separate with
PEX7 having 2 unique accessory proteins, PEX18 and PEX21.
PEX5 and PEX7 receptors with their cargoes dock at a complex
in the peroxisome membrane comprised of PEX14, 13 (and
17 in baker’s yeast). This docking complex is part
of a larger complex ‘the importomer’ which
includes the membrane proteins PEX2,10 and 12. By a mechanism
that remains unknown, matrix proteins traverse the membrane,
probably still associated with their receptor. PEX5 at
least partially traverses the membrane and interacts with
PEX8 on the trans side of the membrane. Subsequently cargo
is unloaded and the receptors recycled, again by an unknown
mechanism that involves PEX4 and 22. Insertion of peroxisome
membrane proteins (PMPs) is less well understood but requires
PEX19, which may function as a receptor/chaperone and PEX3.
In mammals PEX16 is also involved in this process. (see
Brown and Baker 2003 for further details).
Relevant publications
A. Baker & I.A. Sparkes (2005)
Peroxisome protein import: some answers, more questions.
Current Opinion in Plant Biology 8, 640-647.
W.L. Charlton,
B. Johnson, I.A., Graham & A. Baker (2005)
Non-coordinate expression of peroxisome biogenesis, BETA-oxidation
and glyoxylate cycle genes in mature Arabidopsis
plants. Plant Cell Reports 23, 647-653
W.L. Charlton,
K. Matsui, B. Johnson, I.A. Graham and A. Baker (2005)
Salt-induced expression of peroxisome
associated
genes requires components of the ethylene, jasmonate
and ABA signalling pathways. Plant Cell & Environment 28, 513-524.
F.L. Theodolou, K. Job,
S.P.Slocombe, S. Footitt, M. Holdsworth, A. Baker, T.R.Larson
and I.A.Graham (2005)
Jasmonate levels
are reduced in COMATOSE ABC transporter mutants:
implications for transport of jasmonate precursors into
peroxisomes.
Plant Physiology 137, 835-840.
I. A. Sparkes, C. Hawes,
and A. Baker (2005) AtPEX2 and AtPEX10
Are Targeted to Peroxisomes Independently
of
Known Endoplasmic Reticulum Trafficking Routes.
Plant Physiology 139: 690-700
S. Bonsegna, S. P. Slocombe,
L. De Bellis and A. Baker (2005) AtLACS7
interacts with the TPR
domains
of the
PTS1 receptor PEX5. Archives of Biochemistry
and Biophysics in press
L.A. Brown & A.
Baker (2003) Peroxisome Biogenesis
and the role of protein import. Journal of Cellular
and Molecular Medicine 7, 388-400
J. Parkes S. Langer,
A. Hartig & A. Baker
(2003) PTS1-independent targeting of isocitrate lyase
to peroxisomes requires the PTS1 receptor Pex5p. Mol.
Membrane Biol. 20, 61-69
M.Murphy, B. Phillipson,
A. Baker & R. Mullen
(2003) Characterisation of the targeting signal of Arabidopsis
22kDa membrane protein. Plant Physiology 133,
813-828.
Footitt, S., Slocombe,
S. Larner, V. Kurup, S., Wu, Y., Larson, T., Graham,
I. Baker, A, and Holdsworth, M. (2002)
Control of germination and lipid mobilisation by COMATOSE
the arabidopsis homologue of human ALDP. EMBO J.
21, 2912-2922.
I.A.Sparkes &
A. Baker (2002) Peroxisome
Biogenesis in Plants Animals and Yeasts. Enigma and
Variations? Mol. Memb. Biol. 19, 171-185.
E. Lopez-Huertas,
W.L. Charlton, B. Johnson, I.A. Graham & A. Baker
(2000) Stress Induces Peroxisome Biogenesis Genes. EMBO
J. 19, 6770-6777
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