Anomalous Subdiffusion in Fluorescence Photobleaching Recovery: A Monte Carlo Study

Saxton, Michael J.

doi:10.1016/s0006-3495(01)75870-5

Cited by 257 publications

(266 citation statements)

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“…However, when more detailed analyses are carried out, it has been found in many cases that the entire population of molecules is not moving at this reduced rate, as one would expect for movement through a viscous solution, but instead, multiple populations of molecules with different mobilities are present (e.g., Politz et al, 1998;Wachsmuth et al, 2000;Platani et al, 2002;Pederson, 2002). This is consistent with anomalous subdiffusion, where mobility is constrained either by transient binding to and/or collisions with nuclear entities or by corralling within confinement zones, both of which phenomena impede free diffusion and give rise to multiple subpopulations of molecules moving with different mobilities (Feder et al, 1996;Saxton, 2001). …”

Section: Discussionmentioning

confidence: 69%

“…When the log ( 2 /dt) is plotted vs. log dt, the degree of anomalous diffusion can be determined, and information about the obstacle concentration is also obtainable in some cases (Saxton, 1994(Saxton, , 2001Platani et al, 2002). We found that 60S subunit diffusion was indeed anomalous in the nucleoplasm; the log-log plots were linear with a very steep slope ( Figure 6B), instead of the zero slope that would be seen with unconstrained diffusion.…”

Section: Molecular Biology Of the Cell 4808mentioning

confidence: 82%

“…However, the results of these experiments, along with the work of others, suggests a second interpretation, viz., that particle mobility is slowed by encounters with other nuclear structures or particles. This is usually called anomalous diffusion (Saxton, 1994(Saxton, , 2001Feder et al, 1996). Diffusive-like movement has now been observed in the nucleus of live cells for several nuclear proteins, including nucleolar proteins (Pederson, 2000;Misteli, 2001;Pederson, 2001b) as well as poly(A) RNA (Politz et al, 1998.…”

Section: Discussionmentioning

confidence: 99%

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Diffusion-based Transport of Nascent Ribosomes in the Nucleus

Politz

Tuft

Pederson

2003

MBoC

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Although the complex process of ribosome assembly in the nucleolus is beginning to be understood, little is known about how the ribosomal subunits move from the nucleolus to the nuclear membrane for transport to the cytoplasm. We show here that large ribosomal subunits move out from the nucleolus and into the nucleoplasm in all directions, with no evidence of concentrated movement along directed paths. Mobility was slowed compared with that expected in aqueous solution in a manner consistent with anomalous diffusion. Once nucleoplasmic, the subunits moved in the same random manner and also sometimes visited another nucleolus before leaving the nucleus. INTRODUCTIONIn eukaryotes, rRNA transcription and ribosome assembly take place in the nucleolus. Nascent ribosomes then exit the nucleolus and move into the cytoplasm. Multiple ribosomal proteins assemble with rRNA in the nucleolus and may facilitate proper processing of the pre-rRNA primary transcript (Fatica and Tollervey, 2002). Additionally, a significant number of nonribosomal proteins bind to these formative ribosomes in the nucleolus and also in the nucleoplasm after the nascent ribosomal subunits leave the nucleolus Kuersten et al., 2001;Nissan et al., 2002). The binding of particular proteins in a prescribed order is probably necessary for nucleocytoplasmic transport of the processed ribosomal subunits (e.g., Milkereit et al., 2001). The nuclear export of both the large and small ribosomal subunits has been shown to be dependent, at least indirectly, on the Ran-GTPase cycle and the exportin CRM1, and it is likely that CRM1-mediated export of 60S subunits requires the adaptor protein NMD3 (Moy and Silver, 1999;Ho et al., 2000;Gadal et al., 2001;Thomas and Kutay, 2003;Trotta et al., 2003). In situ hybridization experiments in fission yeast have indicated that rRNA may accumulate along short tracks when near the nuclear pores but nonetheless appears to exit from all the pores, not just those near the nucleolus (Léger-Silvestre et al., 1999). In situ hybridization studies in mammalian cells have primarily addressed the distribution of rRNA within the nucleolus (Huang, 2002) rather than the routes of extranucleolar rRNA traffic, because although high signal representing rRNA is routinely detected in both the nucleolus and the cytoplasm, nucleoplasmic signal which might represent ribosomes moving to the nuclear periphery is not easily detectable by in situ hybridization (PuvionDutilleul et al., 1991;Lazdins et al., 1997; J.C.R. Politz, unpublished observations). Therefore, very little is known about the spatial pattern or mechanism of rRNA movement from the nucleolus into the nucleoplasm and then to the nuclear pores for export (Cullen, 2000;Kuersten et al., 2001;Lei and Silver, 2002), although all three classes of eukaryotic RNAs, rRNA, mRNA, and pol III transcripts have been shown to exit from all the nuclear pores (Dworetzky and Feldherr, 1988;Pante et al., 1997;Mattaj and Englmeier, 1998).In previous studies in live cells (Politz et al., 1998, we investigat...

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Section: Discussionmentioning

confidence: 69%

Section: Molecular Biology Of the Cell 4808mentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Diffusion-based Transport of Nascent Ribosomes in the Nucleus

Politz

Tuft

Pederson

2003

MBoC

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“…Special attention has been paid to slow subdiffusive transport for which meansquared displacement is sublinear x 2 (t) ∼ t μ , where μ is the anomalous exponent μ < 1. Subdiffusion is experimentally observed for proteins and lipids on cell membranes [5], RNA molecules in the cells [6], transport in spiny dendrites [7], etc. The major feature of this process is the absence of the characteristic microscopic time scale.…”

Section: Introductionmentioning

confidence: 99%

Subdiffusive master equation with space-dependent anomalous exponent and structural instability

Fedotov

Falconer

2012

Phys. Rev. E

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We derive the fractional master equation with space-dependent anomalous exponent. We analyze the asymptotic behavior of the corresponding lattice model both analytically and by Monte Carlo simulation. We show that the subdiffusive fractional equations with constant anomalous exponent μ in a bounded domain [0,L] are not structurally stable with respect to the nonhomogeneous variations of parameter μ. In particular, the GibbsBoltzmann distribution is no longer the stationary solution of the fractional Fokker-Planck equation whatever the space variation of the exponent might be. We analyze the random distribution of μ in space and find that in the long-time limit, the probability distribution is highly intermediate in space and the behavior is completely dominated by very unlikely events. We show that subdiffusive fractional equations with the nonuniform random distribution of anomalous exponent is an illustration of a "Black Swan," the low probability event of the small value of the anomalous exponent that completely dominates the long-time behavior of subdiffusive systems.

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“…A great deal of information about motion of molecules in living cells has been obtained from intracellular measurements using different experimental techniques [7,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and from simulations [10,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. Experimental data are usually obtained by fluorescence recovery after photobleaching (FRAP) [12-14, 16, 18, 20, 28, 30], fluorescence correlation spectroscopy (FCS) [11-23, 26-27, 29] and single particle tracking (SPT) [15,19,[24][25] techniques.…”

Section: Introductionmentioning

confidence: 99%