E. Denarier et al., NONNEURONAL ISOFORMS OF STOP PROTEIN ARE RESPONSIBLE FOR MICROTUBULE COLD STABILITY IN MAMMALIAN FIBROBLASTS, Proceedings of the National Academy of Sciences of the United Statesof America, 95(11), 1998, pp. 6055-6060
A number of cycling mammalian cells, such as NIH 3T3, contain abundant
subsets of cold-stable microtubules, The origin of such microtubule s
tabilization in nonneuronal cells is unknown, We have previously descr
ibed a neuronal protein, stable tubule-only polypeptide (STOP), that b
inds to microtubules and induces cold stability. We find that NIH 3T3
fibroblasts contain a major 42-kDa isoform of STOP (fibroblastic STOP,
F-STOP), F-STOP contains the central repeats characteristic of brain
STOP but shows extensive deletions of N- and C-terminal protein domain
s that are present in brain STOP. These deletions arise from differenc
es in STOP RNA splicing, Despite such deletions, F-STOP has full micro
tubule stabilizing activity. F-STOP accumulates on cold-stable microtu
bules of interphase arrays and is present on stable microtubules withi
n the mitotic spindle of NIH 3T3 cells, STOP inhibition by microinject
ion of affinity-purified STOP central repeat antibodies into NIH 3T3 c
ells abolishes both interphase and spindle microtubule cold stability.
Similar results were obtained with Rat2 cells. These results show tha
t STOP proteins have nonneuronal isoforms that are responsible for the
microtubule cold stability observed in mammalian fibroblasts.