tailieunhanh - Báo cáo y học: " Modeling the signaling endosome hypothesis: Why a drive to the nucleus is better than a (random) walk"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Modeling the signaling endosome hypothesis: Why a drive to the nucleus is better than a (random) walk | BioMed Central Theoretical Biology and Medical Modelling Research Open Access Modeling the signaling endosome hypothesis Why a drive to the nucleus is better than a random walk Charles L Howe Address Departments of Neuroscience and Neurology Mayo Clinic College of Medicine Guggenheim 442-C 200 1st Street SW Rochester MN 55905 USA Email Charles L Howe - Corresponding author Published 19 October 2005 Received 01 September 2005 Theoretical Biology and Medical Modelling 2005 2 43 doi l742-4682-2-AcCepted 19 October 2005 43 This article is available from http content 2 1 43 2005 Howe licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Information transfer from the plasma membrane to the nucleus is a universal cell biological property. Such information is generally encoded in the form of post-translationally modified protein messengers. Textbook signaling models typically depend upon the diffusion of molecular signals from the site of initiation at the plasma membrane to the site of effector function within the nucleus. However such models fail to consider several critical constraints placed upon diffusion by the cellular milieu including the likelihood of signal termination by dephosphorylation. In contrast signaling associated with retrogradely transported membrane-bounded organelles such as endosomes provides a dephosphorylation-resistant mechanism for the vectorial transmission of molecular signals. We explore the relative efficiencies of signal diffusion versus retrograde transport of signaling endosomes. Results Using large-scale Monte Carlo simulations of diffusing STAT-3 molecules coupled with probabilistic modeling of dephosphorylation kinetics we found that .