Title:
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Establishment and regulation of polar growth in Streptomyces
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A fundamental question in developmental biology is how cells establish polarity, and most strikingly how cells grow polarly. From neuronal dendrites and root hairs to bud emergence and elongation of yeast, broadly conserved pathways control cell polarity in eukaryotes. In contrast, virtually nothing is known about the regulatory mechanisms controlling polar cell growth in prokaryotes. In evolutionary terms, the most ancient form of polar growth is found in the branching hyphae of the filamentous bacteria Streptomyces, and it is clear that the essential coiled-coil protein DivIVA, which forms part of a tip-organising, multiprotein polarisome complex, plays a key role in the control of cell polarity, apical growth and hyphal branching in Streptomyces coelicolor. I identified and characterised two regulatory mechanisms, both reminiscent of aspects of cell polarity control in eukaryotes. First, I show that the mechanistic basis of branch-site selection during hyphal growth in Streptomyces is a novel polarisome splitting mechanism, in which the apical tip polarisome splits to leave behind a small daughter polarisome on the lateral membrane as the tip grows away. This daughter polarisome gradually grows in size, and ultimately initiates the outgrowth of a new branch. Second, I show that the Ser/Thr protein kinase AfsK is part of an apparatus that controls the polarisome complex at the hyphal tip. Activated AfsK directly phosphorylates DivIVA and profoundly alters the subcellular localisation of DivIVA to establish multiple new sites of polar growth. Thereby, AfsK modulates apical growth and lateral branching during normal growth and cell wall stress. I suggest that this is part of a stress response that provides Streptomyces with a mechanism to dismantle the apical growth apparatus at established hyphal tips that encounter problems with cell wall synthesis (for example through exposure to an antibiotic or by hitting a physical obstacle in the soil) and instead direct emergence of new branches elsewhere along the hyphae.
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