Microtubule-based mechanisms determining intracellular organization
Cells require a defined architecture to perform their specific functions. Cellular architecture is discernible in the exterior appearance of different cell types but also in their internal organization. The intracellular architecture of a eukaryotic cell is determined by the complement of organelles with their specific positions and shapes and facilitates the cell’s particular role in the organism. Accordingly, intracellular organization is dynamically altered to adapt to new cellular roles during processes such as development and polarization. In diseased cells, on the other hand, intracellular architecture can be significantly transformed. The remodeling of tumor cells, for instance, precedes metastatic spreading of most cancers. Furthermore, intracellular architecture is adjusted throughout the cell cycle, most obviously during mitosis to allow faithful division of chromosomes and other cellular contents.
To date, only few proteins are known that can bring about the structural changes in organelle shape and positioning necessary for intracellular remodeling.
Intracellular remodeling often involves the microtubule cytoskeleton in addition to membrane-bound organelles. Thus, proteins that associate with both microtubules and organelles may coordinate the reorganization of microtubules and organelles. These linker proteins are therefore promising candidates for new effectors of intracellular remodeling. With a biochemical screening approach we have previously identified new candidate linkers between organelles and microtubules. We showed that the uncharacterized linkers REEP3 and REEP4 govern the distribution of the endoplasmic reticulum (ER) during cell division. REEP3/4 are the first proteins identified that bring about mitotic ER organization in a microtubule-dependent manner.
Research in the lab aims at (1) further elucidating the mechanisms of REEP3/4 function, (2) characterizing the mitotic remodeling of other organelles and (3) uncovering roles of organelle-microtubule linker proteins in cell polarization and differentiation.
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Schlaitz AL, Thompson J, Wong CC, Yates JR and Heald R. REEP3/4 ensure endoplasmic reticulum clearance from metaphase chromatin and proper nuclear envelope architecture. Developmental Cell, 2013.
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