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Persistent directional cell migration requires ion transport proteins as direction sensors and membrane potential differences in order to maintain directedness.

ABSTRACT: BACKGROUND: Ion transport proteins generate small electric fields that can induce directional cell motility; however, little is known about their mechanisms that lead to directedness. We investigated Na, K-ATPase (NaKA) and Na+/H+ exchanger isoforms (NHE1 and 3) in SaOS-2 and Calvarial osteoblasts, which present anode- and cathode- directed motility, during electrotaxis. RESULTS: Significant colocalizations of NaKA with vinculin and pNHE3 with ß-actin were observed to occur at the leading edges of cells. The directedness were attenuated when NaKA or NHE3 was inhibited, confirming their implication in directional sensing. Depending on the perceived direction, a divergent regulation in PIP2 levels as a function of NHE3 and NaKA levels was observed, suggesting that PIP2 may act as a spatiotemporal regulator of the cell membrane during electrotaxis. Moreover, at the same places where pNHE3 accumulates, bubble-shaped H+ clouds were observed, suggesting a physio-mechanical role for NHE3. The cell membrane becomes hyperpolarized at the front and depolarized at the back, which confirms NaKA activity at the leading edge. CONCLUSION: We suggest a novel role for both NaKA and NHE3 that extends beyond ion translocation and conclude that they can act as directional sensors and Vmem as a regulatory cue which maintain the persistent direction in electrotaxis.

SUBMITTER: Ozkucur N

PROVIDER: S-EPMC3042415 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Persistent directional cell migration requires ion transport proteins as direction sensors and membrane potential differences in order to maintain directedness.

Ozkucur Nurdan N Perike Srikanth S Sharma Priyanka P Funk Richard H W RH

BMC cell biology 20110122

<h4>Background</h4>Ion transport proteins generate small electric fields that can induce directional cell motility; however, little is known about their mechanisms that lead to directedness. We investigated Na, K-ATPase (NaKA) and Na+/H+ exchanger isoforms (NHE1 and 3) in SaOS-2 and Calvarial osteoblasts, which present anode- and cathode- directed motility, during electrotaxis.<h4>Results</h4>Significant colocalizations of NaKA with vinculin and pNHE3 with ß-actin were observed to occur at the l ...[more]

PMID: 21255452

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Project description:The Poisson Nernst-Planck (PNP) theory is a simplified continuum model for a wide variety of chemical, physical and biological applications. Its ability of providing quantitative explanation and increasingly qualitative predictions of experimental measurements has earned itself much recognition in the research community. Numerous computational algorithms have been constructed for the solution of the PNP equations. However, in the realistic ion-channel context, no second order convergent PNP algorithm has ever been reported in the literature, due to many numerical obstacles, including discontinuous coefficients, singular charges, geometric singularities, and nonlinear couplings. The present work introduces a number of numerical algorithms to overcome the abovementioned numerical challenges and constructs the first second-order convergent PNP solver in the ion-channel context. First, a Dirichlet to Neumann mapping (DNM) algorithm is designed to alleviate the charge singularity due to the protein structure. Additionally, the matched interface and boundary (MIB) method is reformulated for solving the PNP equations. The MIB method systematically enforces the interface jump conditions and achieves the second order accuracy in the presence of complex geometry and geometric singularities of molecular surfaces. Moreover, two iterative schemes are utilized to deal with the coupled nonlinear equations. Furthermore, extensive and rigorous numerical validations are carried out over a number of geometries, including a sphere, two proteins and an ion channel, to examine the numerical accuracy and convergence order of the present numerical algorithms. Finally, application is considered to a real transmembrane protein, the Gramicidin A channel protein. The performance of the proposed numerical techniques is tested against a number of factors, including mesh sizes, diffusion coefficient profiles, iterative schemes, ion concentrations, and applied voltages. Numerical predictions are compared with experimental measurements.

Project description:Background and purposeThis study aimed to determine the clinical features, diagnosis, and treatment of patients with persistent geotropic (pG) and persistent apogeotropic (pAG) direction-changing positional nystagmus (DCPN).MethodsThis retrospective study included 30 patients with pG-DCPN and 44 patients with pAG-DCPN. All patients underwent neurological and neurotological examinations, including an evaluation of gaze-evoked nystagmus, eye-movement tests, and assessments of limb ataxia and balance, as well as magnetic resonance imaging to exclude central causes. The characteristics of positional nystagmus were detected using the supine roll test (SRT) and bow-and-lean test (BLT). The null point (NP) at which the nystagmus disappeared was determined. All patients were treated with the barbecue maneuver, and treatment efficacy was evaluated immediately, 1 week, and 1 month after treatment.ResultsThe history of diseases associated with atherosclerosis, peripheral vestibular disorders, otological disease, and migraine differed significantly between patients with pG-DCPN and pAG-DCPN. The affected sides of persistent horizontal DCPN can be determined using the SRT and the BLT, while determining the second NP and vestibular function as well as performing an audiological evaluation can be used to assist in identifying the affected side. The efficacy rates immediately and 1 week after treatment with the barbecue maneuver were higher in patients with pAG-DCPN than in patients with pG-DCPN.ConclusionspAG-DCPN was more compatible with the characteristics of cupulolithiasis, and pG-DCPN was more likely to be associated with a light cupula rather than canalolithiasis. pAG-DCPN was more likely to be accompanied by a disease associated with atherosclerosis, while pG-DCPN was often accompanied by autoimmune-related diseases and a history of migraine. The associations between pAG-DCPN, pG-DCPN, and the above-mentioned diseases need to be clarified further. The canalith-repositioning maneuver was effective in patients with pAG-DCPN and ineffective in patients with pG-DCPN, but most cases of pG-DCPN are self-limiting.

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Persistent directional cell migration requires ion transport proteins as direction sensors and membrane potential differences in order to maintain directedness.

Publications

Persistent directional cell migration requires ion transport proteins as direction sensors and membrane potential differences in order to maintain directedness.

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