The major focus of our
laboratory
is to understand the role of compartmentation of enzymes and metabolites
in biological regulation. The organellar localization of metabolic pathways
requires considerable expenditure of metabolic energy for protein targeting,
organelle assembly, and movement of substrates and products across intracellular
membranes. Such expenditures must result in biological efficiencies commensurate
with the investment of biological resources. However, it is not always
clear what advantages are conferred by such compartmentation.
We have focused our attention on
arginine metabolism in Neurospora crassa because it encompasses many of
the compartmental features characteristic of eukaryotic cells. Biosynthesis
of arginine originates in the mitochondria but culminates in the cytosol.
Intermediates and arginine cross both mitochondrial membranes. More than
95% of the intramycelial pool of arginine is sequestered in the vacuoles.
Our hypothesis is that these compartmentation features play a significant
role in the biology of the organism.
We are investigating the metabolic
consequences of relocating the arginine biosynthetic enzymes from the mitochondrial
matrix to the cytosol. In addition, we are examining how variations in
cytosolic arginine concentrations are communicated across the mitochondrial
membranes to coordinately inhibit two enzymes of arginine biosynthesis.
Molecular techniques are being used to construct mutants defective in the
movement of metabolites across intracellular membranes. Control of arginine
degradation is being examined by characterizing the expression, structure
and properties of arginase, the initial catabolic enzyme. The results of
these experiments will provide insight into the function of enzyme and
amino acid compartmentation in eukaryotic cells.
(To find out more about each person's individual project, go to the
Current Lab
Members
page)
Some References
Parra-Gessert L, Koo K, Fajardo J, Weiss RL (1998) Processing
and function of a polyprotein precursor of two mitochondrial proteins in
Neurospora crassa. Journal of Biological Chemistry. 273(14):7972-80
Keenan KA, Weiss RL (1997) Characterization of vacuolar
arginine uptake and amino acid efflux in
Neurospora crassa using cupric ion to permeabilize the plasma
membrane. Fungal Genet Biol. 22(3):177-90
Yu YG, Turner GE, Weiss RL (1996) Acetylglutamate synthase
from Neurospora crassa: structure and
regulation of expression. Molecular Microbiology. 22(3):545-54.
Gessert, S. F., Kim, J. H., Nargang, F. E., Weiss, R. L. (1994)
A Polyprotein Precursor of Two Mitochondrial Enzymes in Neurospora crassa.
The Journal of Biological Chemistry. 269: 8189-8203.
Yu YG, Weiss RL (1992) Arginine transport in mitochondria
of Neurospora crassa. Journal of Biological Chemistry.
267(22):15491-5
Paek YL, Weiss RL (1989) Identification of an arginine carrier
in the vacuolar membrane of
Davis, R. H., Weiss, R. L. (1988) Novel Mechanisms Controlling
Arginine Metabolism in Neurospora. Trends in Biochemical Sciences.
13: 101-104.
Wandinger-Ness, A. U., Weiss, R. W. (1987) A Single Precursor
Protein for Two Separable Mitochondrial Enzymes in Neurospora crassa.
The Journal of Biological Chemistry. 262: 5823-5830.
Borkovich KA, Weiss RL (1987) Relationship between two major
immunoreactive forms of arginase in
Neurospora crassa. Journal of Bacteriology. 169(12):5510-7
Ness SA, Weiss RL (1987) Carboxyl-terminal sequences influence
the import of mitochondrial
Borkovich KA, Weiss RL (1987) Purification and characterization
of arginase from Neurospora crassa. J Biol Chem. 262(15):7081-6
Goodman I, Weiss RL (1986) Control of arginine metabolism
in Neurospora crassa. Role of feedback
inhibition. J Biol Chem. 261(22):10264-70
Zerez CR, Weiss RL, Franklin C, Bowman BJ (1986) The properties
of arginine transport in vacuolar membrane vesicles of Neurospora crassa.
J Biol Chem. 261(19):8877-82
Zerez CR, Weiss RL (1986) Effect of chloramphenicol and
ethidium bromide on the level of ornithine
carbamoyltransferase in Neurospora crassa. J Bacteriol.
166(2):679-82.
Hinde, R. W., Jacobson, J. A., Weiss, R. L., Davis, R. H. (1986)
N-acetyl-L-Glutamate Synthase of Neurospora crassa. The Journal
of Biological Chemistry. 261: 5848-5852.
Wandinger-Ness, A. U., Ness, S. A., Weiss, R. W. (1986)
Simultaneous Purification of Three Mitochondrial Enzymes. The
Journal of Biological Chemistry. 261: 4820-4827.
Wandinger-Ness, A. U., Wolf, E. C., Weiss, R. W., Davis, R. H.
(1985) Acetylglutamate Kinase-Acetylglutamyl-Phosphate Reductase
Complex on Neurospora crassa. The Journal of Biological Chemistry.
260: 5974-5978.
Ness SA, Weiss RL (1985) Carbamoyl-phosphate synthetases
from Neurospora crassa. Immunological
relatedness of the enzymes from Neurospora, bacteria, yeast,
and mammals. J Biol Chem. 260(26):14355-62
Bates M, Weiss RL, Clarke S. (1985) Ornithine transcarbamylase
from Neurospora crassa: purification and
properties. Arch Biochem Biophys 239(1):172-83
Legerton TL, Weiss RL (1984) Mobilization of vacuolar arginine
in Neurospora crassa. Mechanism and
role of glutamine. J Biol Chem. 259(14):8875-9.
Davis, R. H., Weiss, R. L. (1983) Identification of Nonsense
Mutations in Neurospora: Application to the complex arg-6
Locus. Molecular and General Genetics. 192:
46-50.
Wolf, E. C., Weiss, R. L. (1980) Acetylglutamate Kinase.
The Journal of Biological Chemistry. 255: 9189-9195.
Weiss, R. L., Davis, R. H. (1977) Control of Arginine Utilization
in Neurospora. Journal of Bacteriology. 129:
866-873.
Weiss, R. L. (1976) Compartmentation and Control of Arginine Metabolism
in Neurospora. Journal of Bacteriology. 126:
1173-1179.Marathe S., Y. G. Yu, G. E. Turner, C. Palmier, R. L. Weiss
(1998) Multiple Forms of Arginase Are Differentially Expressed from
a Single Locus in Neurospora crassa. Journal of Biological
Chemistry. 273: 29776-29785.
RLW
Home
Neurospora crassa. Journal of Biological Chemistry. 264(13):7285-90.
protein precursors in vivo. Proc Natl Acad Sci U S A.
84(19):6692-6