TPPP/p25 is a brain-specific protein, which induces tubu
lin po
lymerization and microtubu
le(MT) bund
ling and is enriched in Lewy bodies characteristic of Parkinson's disease [Tiri
aacute.gif">n et a
l. (2003)
Proc. Natl. Acad. Sci. U.S.A. 100, 13976-13981]. We identified two human gene sequences, CG1-38and p25
le">, which encoded homo
logous proteins, that we termed p20 and p18, respective
ly. Thesehomo
logous proteins disp
lay 60% identity with tubu
lin po
lymerization promoting protein/p25 (TPPP/p25); however, the N-termina
l segment of TPPP/p25 is missing. They cou
ld be c
lustered into threesubfami
lies present in mamma
ls and other vertebrates. We c
loned, iso
lated, and characterized the structura
land functiona
l properties of the recombinant human proteins at mo
lecu
lar, u
ltrastructura
l, and ce
llu
lar
leve
ls using a number of too
ls. These data revea
led that, whi
le p20 behaved as a disorganized proteinsimi
lar
ly to TPPP/p25, which was described as a f
lexib
le and inherent
ly dynamic protein with a
longunstructured N-termina
l tai
l, p18 was featured in more ordered fashion. TPPP/p25 and p20 specifica
llyattached to MTs causing MT bund
ling both
in vitro and
in vivo; p18 protein did not cross-
link MTs, andit distributed homogeneous
ly within the cytoso
l of the transfected HeLa ce
lls. These data indicate that thetwo shorter homo
logues disp
lay distinct structura
l features that determine their associations to MTs. Theproperties of p20 resemb
le TPPP/p25. The bund
ling activity of these two proteins resu
lts in the stabi
lizationof the microtubu
lar network, which is
like
ly re
lated to their physio
logica
l functions.