Biomedical Engineering Reference
In-Depth Information
Table 5.1.
Regulation and inhibition mechanisms for motors.
Regulator/Inhibitor
Motor
Mechanism
Reference
Physiological Regulators
Autoregulated state, the
converter of one head jams
into the actin binding cleft of
the other
10S Conformation
Smooth Myosin
[73]
May bind somewhere near the
upper lobe, slows ADP release
in a Ca
++
-dependent manner
Tail
Myosin V
[74, 75, 76]
Prevents
microtubule-stimulated ADP
release, structural basis
unknown
Tail
Kinesin
[77]
Competes for binding site on
actin
Troponin/Tropomyosin
Skeletal Myosin
[78]
Extremely high ADP a
nity
causes the motor to spend
most of its time in stall under
cellular conditions
ADP
Myosin VI
[79]
Upon binding of Ca
++
,
calmodulin-like domain folds
into microtubule-binding
region, competing with
microtuble binding
Calmodulin-like Regu-
latory Domain
Kinesin-like Calmod-
ulin Binding Protein
[80]
Non-Physiological Small-molecule Inhibitors
Allosterically inhibits Pi
release
Blebbistatin
Myosin II
[81]
Allosterically blocks
microtubule-stimulated ADP
release
Monastrol
Eg5 (kinesin family)
[82]
Competitive inhibitor of
microtubule binding
Rose Bengal
Kinesin
[83]
Competitive inhibitor of
microtubule binding
Adociasulfate-2
Kinesin
[84]
5.7 Motor Coordination in Cells: The Return of Simple
Models?
Is there any room for the reductionist thinking that motor mechanism re-
searchers are accustomed to in dealing with the problem of how cargo gets to
its destination within cells? Despite the endless combinatorial array of motor
regulatory and cargo-binding mechanisms, several experiments indicate that
the answer is yes. While regulatory and cargo-binding mechanisms are com-
plex and unique to each motor, they can be controlled by simple chemical
signals on the cellular level. This has been clearly demonstrated in pigment
cells. Treatment of these cells with a single chemical signal (such as adrenalin
and caffeine, in the case of fish pigment cells) can induce full-scale aggregation
or dispersion of pigment granules [94].
Kinesin, dynein, and myosin V have all been shown to move the same
organelles in this system, and in fact they are all attached at once [93]. The
attachment of myosin V can be regulated by Calmodulin kinase II, but ki-
