Молекулярно-биологические события, как и любые другие химические реакции, зависят от температуры. Следовательно, должны существовать определенные механизмы, обеспечивающие тонкую подстройку большого числа взаимосвязанных биохимических процессов, и придающие системе устойчивость, надежность (robustness). Без таких подстроечных механизмов и эмбриональное развитие, и поддержание нормальной организации тканей при отклонении температуры от оптимальной было бы невозможно. Тем не менее, исследований на эту тему поразительно мало.

Недавно британские ученые на модели дрозофилы выяснили механизмы термокомпенсации активности сигнального каскада Notch. Напомним, что сигнальный каскад Notch активируется при связывании трансмембранного лиганда Delta (на поверхности соседней клетки) с рецептором Notch, что приводит к протеолитическому отщеплению С-конца Notch, который перемещается в ядро и выступает там в качестве транскрипционного активатора. Однако, существуют механизмы лиганд-независимой регуляции какскада Notch, связанные с эндоцитозом. В одном случае, Notch попадает в лизосомы при участии клатрина и белка Deltex (Dx), что приводит к активации каскада. В другом случае, при участии suppressor of deltex (Su(dx)), и холестерол-богатых мембранных доменов, Notch отправляется в ранние эндосомы, что приводит к его деградации и подавлению каскада. Мутация по Dx является температурно-чувствительной, что привело авторов к идее о его роли в термокомпенсации каскада. Используя различные мутантные производные Notch, они изучили влияние температуры на активность компонентов каскада по отдельности. Выяснилось, что активность Dx не зависит от температуры, тогда как Su(dx)-опосредованный эндоцитоз возрастает при повышении температуры, что приводит к компенсации усиления лиганд-зависимой активности каскада при повышении температуры. Исходя из экспериментальных данных, авторы построили математическую модель каскада, адекватно описывающую поведение каскада как в норме (при разных температурах), так при мутациях. Таким образом, данная работа является важной вехой в изучении механизмов термокомпенсации основных сигнальных каскадов животных.
авторский текст

Картинка из preview к рассматриваемой статье (R6, R7, R9 -точки активации каскада, соответствующие дифференциальным уравнениям в мат. модели каскада). Dx и Su(dx) пути пересекаются при сортировке в ранних эндосомах, что обеспечивается, предположительно, белком Krz.

Источники
preview: Delidakis. Tempering Temperature Changes for Robust Development. Cell 2014, Volume 157, Issue 5, p1010–1012.

статья: Shimizu et al. Compensatory Flux Changes within an Endocytic Trafficking Network Maintain Thermal Robustness of Notch Signaling. Cell 2014, Volume 157, Issue 5, p1160–1174.

Британским врачам (уж точно - не ученым...) надо меньше профанацией в науке заниматься и кто их туда допустил? Сказано - не плодотворной научной работы не существует. Кому нужна термокомпенсация у дрозофилы? Это не научная работа. Если они изучают методы борьбы с насекомыми - то там интересно только одно - дохнет она или нет, и изучать это дело не ученых, а врачей с санэпидемстанции, там ничего сложного нет. А так - это пустой никому не нужный наукоемкий бред - вымогательство называется. Есть вещи стоят дорого, дают не большой, но важный результат - а здесь все наоборот, и это кроме того, что, наверно, какие-то дилетанты, дорвавшиеся до наукоемкой лабораторной методики просто гадят науке - позорят саму ее суть. На коллекцию бабочек - стоит выделять деньги, а на вот такой лабораторный бред, наверно, медиков под а ля они наукой занялись - нет.
Какая НАУЧНАЯ база лежит под такой "тонкой" работой? Или решили пока просто подзаработать, коли методика есть?

Баба дура. Где такие умные как ты работают? Чтобы не зайти туда случайно.

"исследований на эту тему поразительно мало" - то что нужно делать никому не надо, они галактики смотрят.

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Привет! Тема термокомпенсации сигнального каскада Notch интересна мне, спасибо, что подняли ее.
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