Estudio de la función de la proteína asociada a microtúbulos 1B durante el desarrollo neuronal
Author
Tortosa Binacua, Elena
Entity
UAM. Departamento de Biología Molecular; Centro de Biología Molecular Severo Ochoa (CBM)Date
2011-01-21Subjects
Proteínas de los microtúbulos-Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21-01-2011Abstract
XVMAP1B
is a microtubule-associated protein that was discovered as a protein which main role
is to promote tubulin assembly and to stabilize microtubules (MTs). MAP1B has also been
shown to bind actin and to regulate a population of dynamic MTs. MAP1B is expressed
prominently during early stages of neuronal development and it has been implicated in axonal
growth, neuronal migration and axonal guidance. However, MAP1B is still expressed in adult
brain areas with high synaptic plasticity with an unknown function.
In this work we have studied the role of MAP1B in the regulation of MTs and actin dynamics,
and its implication during neuronal developmental stages as axonal elongation and dendritic
spines formation and maturation.
Here we have shown that MAP1B participates in regulating MT dynamics. Our results
indicate that, in the absence of MAP1B, MTs nucleate less and faster. Moreover, we have
presented that MAP1B regulates the binding of some +TIPs to MTs and, in some cases, their
protein level. Moreover, it co-immunoprecipitates with some +TIPs with CAP-Gly domains and
with a brain-enriched EB protein, EB3. This suggests that MAP1B could form a complex with
these +TIPs and regulate their behavior thereby contributing to the modulation of MT dynamic.
Moreover, we have presented evidences that MAP1B regulates Rho-GTPases activity by
binding the Rac1-GEF Tiam1 and the RhoA-GEF GEF-H1. This binding takes place during early
neuronal development and in adult stages. In this way, neurons lacking MAP1B show a
decrease in Rac1 and cdc42 activity, and an increase in RhoA activity. According with this, in
the absence of MAP1B the phosphorylation levels of some proteins activated by these Rho-
GTPases are altered. This alteration in Rho-GTPases activity could explain the diminution in
axonal elongation.
In mature neurons, we have provided evidences that MAP1B is present in some dendritic
spines in which development it is implicated. In agreement with this, neurons obtained from
MAP1B-deficient mice show a decrease in density of mature dendritic spines and an increase of
immature filopodia-like protrusions. Although these neurons show normal passive membrane
properties, action potential properties and firing rates, we didn`t observed any LTP-induction.
The morphological alterations observed in dendritic protrusion in neurons lacking MAP1B could
be explained by the Rho-GTPases alterations described previously.
Taken together, these results define a new and important function of MAP1B in the
regulation of actin and tubulin cytoskeleton dynamics during neuronal development and maturation.
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