Title: Cellular motility
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3Cellular motility
Trypanosomes are vigorous swimmers, moving with a
forward velocity as high as 20 mm/s, and are
capable of highly directional cell motility
4Parasite and the avoidance of immune system
-Antigenic variation -Immuno-suppression
Long term persistence of an infecting population
Survival of individual cells During the
emergence of specific humoral immune response
-Clearance of surface bound antibodies
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61 Antibody-VSG complexes are sorted on the cell
surface prior to localized endocytosis
Accumulation of the VSGs at the posterior end of
the cell before endocytosis via the flagellar
pocket and into the the lysosomes
7IgG-VSG removal, 1 movement to the posterior end
of the cell, 2 entry in the flagellar pocket
and 3 endocytosis are characterized by distinct
temperature dependencies
18oC
24oC
12oC
Accumulation occurs at temperature ranging from
12oC-37oC
6oC
37oC
37oC
24oC
18oC
12oC
Entry impeded at lower temperatures
6oC
37oC
24oC
18oC
12oC
6oC
8What causes the movement of IgG-VSG to the
posterior end of the cell?
9The plasma membrane is a very dynamic system
10Endocytosis
Cellular motility
Clathrin heavy chain knockdown Clh RNAi
FLA1 knockdown flaIRNAi
112 Sorting of antibody-VSG complexes on the cell
surface is independent of endocytosis but
requires cellular mobility
Clathrin heavy chain knockdown-No endocytosis
FLA1 knockdown
12DNAI1 knockdown swimming in backward motion
Actin knockdown
procyclics
bloodstreams
133 Extrinsic hydrodynamic flow forces can sort
proteins at the cell surfaces
The size of antibody-VSG complexes determines
the kinetic of sorting
Like a Sail !!!
TAC A aggregate of two murine IgG1 monoclonal
antibodies held in a tetra meric array by 2 rat
anti-IgG1.
14Hydrodynamic flow Forces can drag VSG-IgG within
the surface coat
15The removal of antibodies from the cell surface
renders T. brucei resistant to complement-mediated
lysis.
16T. brucei has evolved a subtle defense strategy ,
in which directional cell motility and plasma
membrane recycling function cooperatively in the
removal host antibodies from the cell surface.