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Jul 27, 2021 · The TOL Patient Portal (also referred to as "TRICARE Online" or "TOL") is the current secure patient portal that gives registered users access to online health care information and services at military hospitals and clinics. Schedule, change, view, or cancel appointments at your military hospital or clinic.

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The TOL Patient Portal (also referred to as "TRICARE Online" or "TOL") is the current secure patient portal that gives registered users access to online health care information and services at military hospitals and clinics.

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Abstract

Rho-GTPase stabilizes microtubules that are oriented towards the leading edge in serum-starved 3T3 fibroblasts through an unknown mechanism. We used a Rho-effector domain screen to identify mDia as a downstream Rho effector involved in microtubule stabilization.

Main

Microtubules are essential for the polarization of many cell types. When microtubules are depolymerized by drugs, cells lose their polarity and retract their processes 1, 2. Loss of cell polarity is paralleled by alterations in the assembly of membrane-localized actin and in the redistribution of cytoplasmic organelles 2, 3.

Results

To screen Rho-effector domain mutants, we used serum-starved NIH 3T3 cells, which have almost no stable Glu microtubules, but make stable Glu microtubules upon addition of serum or LPA or by introducing constitutively active G14VRhoA 16, 17, 18.

Discussion

We have identified mDia as the first Rho effector to be implicated in regulating microtubule stability in cells. Our results show that mDia induces stable microtubules that are capped, and indicates that mDia may promote this microtubule capping by directly binding to microtubules.

Methods

NIH-3T3 cells were cultured in DMEM and calf serum as described 38. Cells on acid-washed coverslips were grown to confluence for 2 days and transferred to serum-free medium (SFM) for 48 h as described 17, except that SFM contained only 1 mg ml −1 fatty-acid-free BSA (Sigma).

Acknowledgements

We thank R. Liem and J. Lessard for providing antibodies, and R. Treisman, L. Lim and K. Kaibuchi for providing DNA constructs. We thank F. Chang for helpful suggestions about mDia. This work was supported by grants from the A.C.S. and the N.I.H. (to G.G.G.). A.F.P. was supported by a fellowship from the Fonds de la Recherche en Santé du Québec.

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What is the megalin protein?

In the kidney, megalin, a large glycosylated protein of 600 kDa sharing structural similarities with the endocytic receptors of the LDL receptor family, binds to cubilin and promotes its endocytosis and that of its ligands 2, 3, 10. Imerslund–Gräsbeck syndrome or juvenile megaloblastic anaemia 1 ...