Size regulation of multiple organelles competing for a limiting subunit pool

Abstract

How cells regulate the size of intracellular structures and organelles is a longstanding question. Recent experiments suggest that size control of intracellular structures is achieved through the depletion of a limiting subunit pool in the cytoplasm. While the limiting pool model ensures organelle-to-cell size scaling, it does not provide a mechanism for robust size control of multiple co-existing structures. Here we develop a generalized theory for size-dependent growth of intracellular structures to demonstrate that robust size control of multiple intracellular structures, competing for a limiting subunit pool, is achieved via a negative feedback between the growth rate and the size of the individual structure. This design principle captures size maintenance of a wide variety of subcellular structures, from cytoskeletal filaments to three-dimensional organelles. We identify the feedback motifs for structure size regulation based on known molecular processes, and compare our theory to existing models of size regulation in biological assemblies. Furthermore, we show that positive feedback between structure size and growth rate can lead to bistable size distribution and spontaneous size selection.

The flagellar length control system: exploring the physical biology of organelle size

“…Once the two flagella reach equal length, neither has an advantage over the other and so they both grow out together, with this growth requiring synthesis of new precursor protein (Coyne and Rosenbaum 1970). Simulations of the steady state model employing a 1/L dependence of IFT on length confirm this conceptual view (Marshall and Rosenbaum 2001, Ludington et al 2012, Banerjee and Banerjee 2022 and show that the long-zero phenomenon, which might appear to involve some complex process of length measurement and information exchange between flagella, actually can be explained just on the basis of competition for a common pool of tubulin.…”

“…In particular, a basic mechanistic question is whether tubulin is added or removed one dimer at a time. This is the assumption made in a number of recently formulated stochastic models for flagellar length (Datta et al 2020, Patra et al 2020, Banerjee and Banerjee 2022. These three studies analyzed distinct length control schemes, ranging from the 1/L dependent IFT assumed based on empirical data (Banerjee and Banerjee 2022), a time of flight model (Patra et al 2020), and a length-dependent disassembly model (Datta et al 2020).…”

Catalytic growth in a shared enzyme pool ensures robust control of centrosome size

“…2D), with the steady-state size given by V = k + N δv/(k − + 2k + ). While this growth model captures centrosome size equality and centrosome size scaling with cell size (18), the resulting growth curve is non-sigmoidal, in contrast to experimental data in C. elegans (8,13).…”

“…While this model quantitatively captures experimentally observed sigmoidal growth dynamics and the scaling of centrosome size with cell size, autocatalytic growth of centrosome pairs can induce significant size fluctuations. In recent work, we have shown that autocatalytic growth of multiple organelles in a shared pool of subunits results in organelle size inequality (18). This result is particularly relevant for understanding centrosome growth, as centrosome pairs grow from a shared pool of components during centrosome maturation (13).…”

“…We then systematically investigate different models of centrosome size control based on known molecular design principles for centrosome assembly (10). In particular, a model for centriole-localized assembly and spatially distributed disassembly (18) ensures robust equality of centrosome size, while failing to capture sigmoidal growth curve as observed experimentally (13). Based on recent experiments uncovering the molecular components of centrosome assembly, we propose a new model of catalytic growth of centrosomes in a shared pool of enzymes.…”