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A 17kd histidine rich (31
histidine out of 118 aminoacids) actin binding protein from Dictyostelium
discoideum (Scheel
et al, 1989).
The protein is
concentrated at the cell cortex, generally coinciding with F-actin.
Probably because of the high histidine content the protein binds to actin
in a pH sensitive manner (like cofilin), and undergoes a large pH-dependent
change (Houliston et
al, 2002). Hisactophilin
induces actin polymerization even in the absence of Mg2+
or K+ at low pH but this effect is less
at higher pH within the physiological range. The sequence of hisactophilin
bears no obvious sequence homology to any known actin binding protein (Scheel
et al, 1989),
but the structure is similar to interleukin-1b
and the fibroblast growth factor (Habazettl
et al, 1992),
(as well as certain plant lectins). The structure of hisactophilin is a
three-fold symmetrical b-barrel
(Habazettl et al,
1992). Two forms of
hisactophilin exist (HsI nad HsII), both are myristoylated and
phosphorylatable on threonine and serine (Hanakam
et al, 1995).
The fact that the protein is membrane associated (Behrisch
et al, 1995,
Hanakam et al,
1995; Nauman
et al, 1996)
suggests that the function of hisactophilin is to serve as a link between the
cortical actin cytoskeleton and the membrane. It is surprising therefore
that cells in which the hisactophilin is knocked out lack any phenotype, even
under conditions designed to stress the cell so that any slight phenotype may be
easier to detect (Ponte
et al, 2000).
These authors (Ponte
et al, 2000)
suggest that a phenotype may be found if the cells were grown at low pH as this
protein is so pH sensitive, however Dictyostelium can maintain pHi
at about 7.5 in media of a range of pH values so more sophisticated
manipulations (Van
Duijn & Inouye, 1991)
will be required to test this. Another ABP, ponticulin is
also likely to function as a major membrane-actin link and so it would be
interesting to test for hisactophilin, ponticulin double knockout.
References:-
Behrisch,
A., C. Dietrich, et al. (1995). “The
actin-binding protein hisactophilin binds in vitro to partially charged
membranes and mediates actin coupling to membranes.”
Biochemistry 34, 15182-15190.
Habazettl,
J., Gondol, D., Wiltscheck, R., Otlewski, J., Schleicher, M. & Holak, T.A.
(1992). "Structure of hisactophilin is similar to interleukin-1b and
fibroblast growth factor. Nature, 359, 855-858.
Hammond
MS. Houliston RS. & Meiering EM. (1998). "Two-dimensional 1H and 15N
NMR titration studies of hisactophilin." Biochemistry & Cell
Biology. 76(2-3) 294-301.
Hanakam,
F., Eckerskorn, C., Lottspeich, F., Muller-Tabenberger, A., Schafer, W. and
Gerisch, G. (1995). "The pH-sensitive actin-binding protein Histactophilin
of Dictyostelium exists in two isoforms which both are myristoylated and
distributed between plasma membrane and cytoplasm. J.Biol.Chem. 270,
596-602.
Houliston,
R. S., Liu, C., Singh, L. M. R. & Meiering, E. M. (2002) pH and urea
dependence of amide hydrogen-deuterium exchange rates in the b-trefoil
protein hisactophilin., Biochemistry. 41, 1182-1194.
Ponte,
E., Rivero, F., Fechheimer, M., Noegel, A.A., & Bozzaro, S. (2000).
"Severe developmental defects in Dictyostelium discoidium null
mutants for actin-binding proteins." Mech.Development 91,
153-161.
Nauman,
C., Dietrich, C., Behrisch, A., Bayerl, T.M. SChleicher, M., Bucknall, D. &
Sackman, E. (1996). "Hisactophilin mediated binding of actin to lip
lamellae - a neutron reflectivity study of protein membrane
coupling." Biophys. J. 71, 811-823.
Scheel,
J., Ziegelbauer, K., Kupke, T., Humbel, B.M., Noegel, A.A., Gerisch, G. &
Schleicher, M. (1989). "Histactophilin, a histidine-rich actin-binding
protein from Dictyostelium discoideum. " J.Biol.Chem. 264(5),
2832-2839.
Van
Duijn, B. & Inouye, K. (1991). "Regulation of movement speed by
intracellular pH during Dictyostelium discoideum chemotaxis." PNAS
USA 88, 4951-4955.
Poppenborg L. Friehs K.
& Flaschel E. (1997). "The green fluorescent protein is a versatile
reporter for bioprocess monitoring." Journal of Biotechnology. 58(2)
79-88.
Hanakam F. Gerisch G.
Lotz S. Alt T. & Seelig A. (1996) "Binding of hisactophilin I and II to
lipid membranes is controlled by a pH-dependent myristoyl-histidine
switch." Biochemistry. 35(34) 11036-11044.
Stoeckelhuber M. Noegel
AA. Eckerskorn C. Kohler J. Rieger D. & Schleicher M. (1996) "Structure/function
studies on the pH-dependent actin-binding protein hisactophilin in Dictyostelium
mutants. J.Cell Sci. 109(7), 1825-1835
Hanakam F. Albrecht R.
Eckerskorn C. Matzner M. & Gerish G. (1996) "Myristoylated and non-myristoylated
forms of the pH sensor protein hisactophilin II: Intracellular shuttling to
plasma membrane and nucleus monitored in real time by a fusion with green
fluorescent protein." EMBO Journal. 15(12), 2935-2943.
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