1

!"## %&'#'() *+,-

*./.,-
0"1234" /5 !)2'67"#"2'8


9&#:;"82 <66";=#) >4'; ?34" @3=38&26

Subunits mixeu togethei at a concentiation gieatei than the 14&2&1:# 1'81"824:2&'8
A!1B will exhibit an initial lag phase (uue to nucleation) followeu by a giowth phase
until the Cc is ieacheu (steauy state). At the Cc, iate of auuition (on iate) anu loss
(off iate) is equal anu the system is at equilibiium. If the concentiation of fiee
subunit uiops below the Cc, then uepolymeiization will occui.

9'4 CD?6 '8#) :8E 6);;"24&1 63=38&26 AF)G'2F"2&1:#B H 2F" 4:2" '> (4'I2FJ6F4&87&8(
:2 ='2F "8E6 '> : >&#:;"82 &6 2F" 6:;".

0n iate= kon*concentiation of subunit (C)
0ff iate=koff
!1K7'>>J7'8K,JL:66'1&:2&'8

CD?6 '8#) :8E :6);;"24&1 63=38&26
Bue to asymmetiy of the subunits anu confoimational changes of the subunits in the
filament, the filament enus polymeiize anu uepolymeiize at uiffeience iates.
Bowevei, the bonus foimeu aie the same so the fiee eneigy anu Keq aie the same.
Theiefoie, the !1 ;362 =" 2F" 6:;" :2 ='2F "8E6 anu the G#36 "8E F:6 : F&(F"4
7'8 :8E 7'>> A;'4" E)8:;&1B :8E 2F" ;&836 "8E F:6 : #'I"4 7'8 :8E 7'>> A#"66
E)8:;&1B. At any given concentiation, ='2F "8E6 :4" "&2F"4 6F4&87&8( A="#'I 2F"
!1B '4 (4'I&8( A:='M" 2F" !1B.
Cc (-)=Cc (+)
Koff (-)Kon(-)=Koff (+)Kon(+)

CD?6H CN?6 :8E :6);;"24&1 63=38&26
In this situation theie aie two foims of each subunit: NBP-bounu (B foim) anu NTP-
bounu (T foim). In a cell, fiee subunits will be in the T foim because |ATPj>>>|ABPj.
A subunit in a filament will hyuiolyze the NTP to NBP aftei a ceitain amount of time.
The T foim has a highei affinity foi the filament (high on iate) than the B foim (high
off iate).

!1AN >'4;BO!1AD >'4;B

These chaiacteiistics leau to fast T foim subunit auuition at the plus enu anu B foim
subunit ielease at the minus enu.

N4":E;&##&8( occuis at a subunit concentiation between the Cc (+enu) anu the Cc (-enu)
so that the plus enu of a filament is giowing while the minus enu is shiinking.

2
D)8:;&1 &862:=&#&2) uesciibes the scenaiio when the plus enu of one filament is giowing
while the plus enu of anothei filament is shiinking simultaneously. The giowing filaments
have a PN? Q1:GR at the plus enu that makes them iesistant to shiinking. The shiinking
filaments have subunits containing uBP at the plus enu which aie much moie likely to
uepolymeiize than uTP subunits. If a filament loses the uTP cap, it can iapiuly switch fiom
giowing to shiinking (this is calleu 1:2:624'GF"). If a shiinking filament can binu a uTP-
containing subunit anu ieestablish the uTP cap, it can stait giowing again (this is calleu
4"613").

<12&8 is believeu to mainly unueigo tieaumilling !" $!$%. S&14'23=3#"6 uefinitely exhibit
uynamic instability !" $!$% anu theie is also eviuence foi tieaumilling.

T"(3#:2&'8 '> 9&#:;"82 D)8:;&16

D43(6 that altei filament uynamics aie useful foi lab anu clinical applications. The uiugs
can binu fiee subunits oi binu plus enus to pievent polymeiization 0R binu anu stabilize
filaments to pievent uisassembly.

In a cell, pioteins iefeiieu to as ;&14'23=3#" :66'1&:2"E G4'2"&86 AS<?@B oi pioteins
with :12&8 =&8E&8( E';:&86 A<%D6B binu to filaments anu iegulate the uynamics.

,. 9&#:;"82 U4(:8&V&8( 1"82"46
a. The ;&14'23=3#" '4(:8&V&8( 1"82"4 ASNU!B (aka centiosome oi spinule pole
bouy) oiganizes all (oi most) of the minus enus in a cell. NT0Cs consist of a paii of
peipenuiculai centiioles (maue of tubulin filaments in a 1S+1u+1u aiiangement) anu a
G"4&1"824&'#:4 ;:24&W A?!SB that contains (:;;:523=3#&8 4&8( 1';G#"W"6 that seive as
a template foi miciotubule foimation (1S gamma tubulin molecules binu to 1S tubulin
uimeis on the alpha siue). Niciotubules can still oiganize in cell without (oi missing) an
NT0C using the motoi piotein uynein anu othei activities which can clustei minus enus
togethei.
b. The :12&854"#:2"E G4'2"&8 *JX A<4G*JXB complex nucleates actin polymeiization
at minus enus. These nucleate filaments &' "%$% oi along the siues of pieviously foimeu
filaments to foim a web.
c. 9'4;&86 binu the plus enu of actin filaments anu nucleate filament giowth by
encouiaging the binuing of a new subunit. The "whiskeis" attiact new actin monomeis via
a piotein that binus actin monomeis (piofilin).