Flagellar Length Control in Chlamydomonas: The Role of Intraflagellar Transport and Turnover

细胞如何调节细胞器大小是细胞生物学的一个基本问题。在这个项目中，真核鞭毛将被用作研究细胞器大小调节的模型系统，通过减少测量大小的问题到一个维度：长度。鞭毛不断更替，长度控制机制必须平衡组装和拆卸的速度，以保持稳定的长度。人们提出了几个模型来解释这种平衡。一个模型依赖于鞭毛内运输（IFT）固有的长度依赖性，这是一个发生在鞭毛内的主动运输过程。根据先前的研究，我们预测随着鞭毛长度的增加，鞭毛的运输效率会降低，导致在一个特定的长度上出现一个组装和拆卸之间的平衡点。另一个模型提出，长度是由一个长度传感器耦合到一个反馈控制系统调节。本项目将通过检验鞭毛长度突变的机制基础来检验这些模型。平衡点模型预测这些突变体一定会影响转运或周转。遗传学和显微镜的结合将用于测试长度改变的突变是否可以完全用周转率或运输率的变化来解释。该项目将为本科生和研究生提供研究培训。

How cells regulate organelle size is a fundamental question in cell biology. In this project the eukaryotic flagellum will be used as a model system for studies of organelle size regulation, by reducing the problem of measuring size to a single dimension: length. Flagella undergo continuous turnover, and the length control mechanism must balance the rates of assembly and disassembly to maintain a steady-state length. Several models have been proposed to explain this balance. One model relies on the inherent length-dependence of intraflagellar transport (IFT), an active transport process that occurs within flagella. Based on prior studies of IFT, it is predicted that the efficiency of transport will decrease as flagellar length increases, leading to a balance-point between assembly and disassembly occurring at a unique length. An alternative model proposes that length is regulated by a length-sensor coupled to a feedback control system. This project will test these models by examining the mechanistic basis of flagellar length mutants. The balance point model predicts that such mutants must affect either transport or turnover. A combination of genetics and microscopy will be used to test whether length-altering mutants can be entirely explained by changes in the rates of turnover or transport. This project will provide research training for undergraduate and graduate students.