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La organización a nanoescala del erizo es esencial para la señalización de largo alcance
Neha Vyas1, Debanjan Goswami, A Manonmani
1National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560 065, India.
Cell
|July 1, 2008
Resumen
La señalización de Hedgehog (Hh) se basa en su organización en oligómeros a nanoescala y grupos visibles, que interactúan con los proteoglicanos de sulfato de heparan (HSPG) para la función paracrina. Las mutaciones interrumpen esta organización, lo que lleva a la señalización autocrina y a una actividad paracrina deteriorada.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología del desarrollo Biología del desarrollo.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las proteínas Hedgehog (Hh) son moléculas de señalización críticas en el patrón de los tejidos.
- La activación de la señalización Hh ocurre en las células que expresan Patched (Ptc).
- La señalización paracrina requiere un transporte de largo alcance, que involucra a los proteoglicanos de sulfato de heparán (HSPG).
Objetivo del estudio:
- Para investigar la organización de las variantes funcionales de Hedgehog (Hh) con etiqueta fluorescente en las células vivas.
- Comprender la relación entre la organización Hh, la interacción HSPG y la función de señalización.
- Para aclarar el papel de los dominios Hh específicos en la oligomerización y el transporte.
Principales métodos:
- Se utilizaron variantes de erizo (Hh) etiquetadas con fluorescencia.
- Se emplearon imágenes ópticas y microscopía de transferencia de energía de resonancia de Förster (FRET).
- Se realizaron estudios de mutación guiados por bioinformática.
Principales resultados:
- La superficie celular Hh forma oligómeros subópticos, concentrados en racimos visibles colocalizados con HSPGs.
- Una mutación en un residuo de lisina conservado interrumpe la oligomerización Hh y la interacción HSPG.
- La isoforma Hh mutada exhibe competencia de señalización autocrina pero carece de capacidad de señalización paracrina.
Conclusiones:
- Hedgehog (Hh) exhibe una organización jerárquica desde oligómeros a nanoescala hasta grupos visibles.
- Esta organización es crucial para la interacción de Hh con los HSPG y la señalización paracrina.
- Las características estructurales específicas dictan la capacidad de Hh para participar en la señalización de largo alcance versus local.
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