Profilins as regulators of actin dynamics

Schlüter, Kathrin; Jockusch, Brigitte M.; Rothkegel, Martin

doi:10.1016/s0167-4889(97)00100-6

Cited by 186 publications

(160 citation statements)

References 130 publications

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“…Biochemical studies revealed that PFN1 and PFN2a have comparable affinities for actin (reviewed in ref. 24). Hence, rather than being based on differences in direct profilin-actin interaction, such diverse variability may concern differential affinities for the profilin partners that are also involved in regulating the actin dynamics in neurons; for example, proteins interacting with the polyproline binding site on profilins.…”

Section: Discussionmentioning

confidence: 99%

Fine-tuning of neuronal architecture requires two profilin isoforms

Michaelsen

Murk

Zagrebelsky

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Two profilin isoforms (PFN1 and PFN2a) are expressed in the mammalian brain. Although profilins are essential for regulating actin dynamics in general, the specific role of these isoforms in neurons has remained elusive. We show that knockdown of the neuron-specific PFN2a results in a significant reduction in dendrite complexity and spine numbers of hippocampal neurons. Overexpression of PFN1 in PFN2a-deficient neurons prevents the loss of spines but does not restore dendritic complexity. Furthermore, we show that profilins are involved in differentially regulating actin dynamics downstream of the pan-neurotrophin receptor (p75 NTR ), a receptor engaged in modulating neuronal morphology. Overexpression of PFN2a restores the morphological changes in dendrites caused by p75 NTR overexpression, whereas PFN1 restores the normal spine density. Our data assign specific functions to the two PFN isoforms, possibly attributable to different affinities for potent effectors also involved in actin dynamics, and suggest that they are important for the signal-dependent finetuning of neuronal architecture.N euronal plasticity depends on functional changes at synapses and, additionally, on the spatial and temporal modulation of neuronal architecture, which is induced by the transmission of external signals to the cytoskeleton. Among the proteins engaged in the organization of the actin cytoskeleton are profilins (1) that bind to monomeric actin, polyproline-stretch proteins, and membranebound phospholipids (reviewed in ref.2). In the mammalian brain, two different profilin isoforms are found: profilin 1 (PFN1), which is ubiquitously expressed in all eukaryotic cells, and profilin 2a (PFN2a), which is tissue-restricted and shows its highest expression level in the brain (3, 4). The cell-and tissue-specific role of profilins remains poorly understood. In particular, the precise function of neuronal PFN2a is still unclear. Recent evidence points to pre-and postsynaptic functions of both isoforms. Experiments with cultured hippocampal neurons revealed activity-dependent targeting of PFN1 (5) and PFN2a (6) into spines of excitatory neurons. Furthermore, Lamprecht et al. (7) demonstrated a stimulus-dependent accumulation of profilin, without isoform specification, in spines of neurons in the rat amygdala. In addition, NMDA receptor activation was seen to correlate with changes in spine morphology, a process apparently involving PFN2a, RhoA, and the RhoA-specific kinase ROCK (8). In contrast, data derived from a KO mouse indicate that PFN2a acts presynaptically, by controlling vesicle exocytosis and presynaptic excitability (9). The aim of the current study was to unravel the physiological role of PFN2a in regulating dendrite morphology and spine stability of mature pyramidal neurons. We used a loss-of-function approach inducing RNAimediated knockdown of PFN2a in hippocampal neurons. Furthermore, we investigated whether PFN2a might be involved in the regulation of actin dynamics downstream of known effectors of neuronal morphology, su...

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Section: Discussionmentioning

confidence: 99%

Fine-tuning of neuronal architecture requires two profilin isoforms

Michaelsen

Murk

Zagrebelsky

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Profilin is a G-actin binding protein that was first discovered in a 1:1 complex with actin in extracts from spleen (Carlsson et al, 1977). It also interacts with poly-Lproline (PLP) and polyphosphoinositides (Sun et al, 1995;Schlüter et al, 1997). Profilin has been found in organisms from all eukaryotic kingdoms and plays a significant role in regulating the dynamics of the actin cytoskeleton (reviewed in Sun et al, 1995;Schlüter et al, 1997;Staiger et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…The Plant Cell regulating the dynamics of the actin cytoskeleton (reviewed in Sun et al, 1995;Schlüter et al, 1997;Staiger et al, 1997). There are, however, conflicting data concerning the activities of profilin in living cells.…”

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confidence: 99%

Pollen Profilin Function Depends on Interaction with Proline-Rich Motifs

et al. 1998

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The actin binding protein profilin has dramatic effects on actin polymerization in vitro and in living cells. Plants have large multigene families encoding profilins, and many cells or tissues can express multiple profilin isoforms. Recently, we characterized several profilin isoforms from maize pollen for their ability to alter cytoarchitecture when microinjected into living plant cells and for their association with poly-L -proline and monomeric actin from maize pollen. In this study, we characterize a new profilin isoform from maize, which has been designated ZmPRO4, that is expressed predominantly in endosperm but is also found at low levels in all tissues examined, including mature and germinated pollen. The affinity of ZmPRO4 for monomeric actin, which was measured by two independent methods, is similar to that of the three profilin isoforms previously identified in pollen. In contrast, the affinity of ZmPRO4 for poly-L -proline is nearly twofold higher than that of native pollen profilin and the other recombinant profilin isoforms. When ZmPRO4 was microinjected into plant cells, the effect on actin-dependent nuclear position was significantly more rapid than that of another pollen profilin isoform, ZmPRO1. A gain-of-function mutant (ZmPRO1-Y6F) was created and found to enhance poly-L -proline binding activity and to disrupt cytoarchitecture as effectively as ZmPRO4. In this study, we demonstrate that profilin isoforms expressed in a single cell can have different effects on actin in living cells and that the poly-L -proline binding function of profilin may have important consequences for the regulation of actin cytoskeletal dynamics in plant cells. INTRODUCTIONThe male gametes of plants are delivered to the ovule by a unique mode of motility that is dependent on cellular morphogenesis of the pollen grain (reviewed in Bedinger and Edgerton, 1989;Mascarenhas, 1993;Taylor and Hepler, 1997). Mature pollen is a haploid multicellular structure consisting of a large vegetative cell and one generative cell or two sperm cells. The sperm are derived from a mitotic division of the generative cell that occurs before pollen maturation or during pollen tube extension. When a pollen grain lands on a receptive stigma, the vegetative cell forms a tipgrowing protuberance, the pollen tube, that extends down the transmitting tissue of the style toward the ovule. Remarkably, the growth rate of the maize pollen tube can exceed 1 cm/hr (Bedinger, 1992). The pollen tube delivers the sperm cells to the embryo sac, where they are deposited to fuse with the egg cell and central cell.Both pollen germination and pollen tube elongation are dependent on the actin cytoskeleton, as determined through studies with cytochalasins (reviewed in Pierson and Cresti, 1992;Taylor and Hepler, 1997). The actin cytoskeleton in pollen is highly dynamic, and dramatic rearrangements occur during pollen germination. Actin microfilaments focus on the germination aperture(s) before generation of the pollen tube and become arranged in long axial bundles t...

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“…mDia, another Rho effector, is also involved in stress fiber formation downstream of Rho activation (11), possibly by regulating actin polymerization and focal adhesion turnover through its association with profilin (12,13) and src-tyrosine-kinase (14), respectively.…”

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Cooperative effects of Rho and mechanical stretch on stress fiber organization

Kaunas

Nguyen

Usami

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

381

417

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The small GTPase Rho regulates the formation of actin stress fibers in adherent cells through activation of its effector proteins Rhokinase and mDia. We found in bovine aortic endothelial cells that inhibitions of Rho, Rho-kinase, and mDia (with C3, Y27632, and F1F2⌬1, respectively) suppressed stress fiber formation, but fibers appeared after 10% cyclic uniaxial stretch (1-Hz frequency). In contrast to the predominately perpendicular alignment of stress fibers to the stretch direction in normal cells, the stress fibers in cells with Rho pathway inhibition became oriented parallel to the stretch direction. In cells with normal Rho activity, the extent of perpendicular orientation of stress fibers depended on the magnitude of stretch. Expressing active RhoV14 plasmid in these cells enhanced the stretch-induced stress fiber orientation by an extent equivalent to an additional Ϸ3% stretch. This augmentation of the stretch-induced perpendicular orientation by RhoV14 was blocked by Y27632 and by F1F2⌬1. Thus, the activity of the Rho pathway plays a critical role in determining both the direction and extent of stretch-induced stress fiber orientation in bovine aortic endothelial cells. Our results demonstrate that the stretch-induced stress fiber orientation is a function of the interplay between Rho pathway activity and the magnitude of stretching.cytoskeletal dynamics ͉ endothelial cells ͉ mechanotransduction ͉ Rho-kinase T he tension generated by contraction of adherent cells against their underlying surface results in an internal stress field that depends on the organization of the cytoskeleton and the associated adhesive contacts (see ref. 1 for review). Intracellular forces have an important role in cellular functions such as migration, proliferation, apoptosis, differentiation, and gene expression (see refs. 2-4 for reviews). Actin stress fibers, which are formed in response to cell contraction (5), consist of bundles of actin microfilaments cross-linked by ␣-actinin, myosin, myosin light-chain, tropomyosin, and other proteins arranged in a manner similar to that in muscle sarcomeres (6). Stress fibers represent the main contractile apparatus in non-muscle cells (7) and are the primary structures associated with intracellular tension. Stress fibers terminate at focal adhesions, which attach the cell to the extracellular matrix (8). Isometric contraction of a cell would result in tension development in the stress fibers, which are anchored at their ends.The activation of the small GTPase Rho leads to stress fiber assembly (9) and cell contraction by means of myosin light chain phosphorylation (5), which is regulated by Rho-kinase, a downstream effector of Rho (10). mDia, another Rho effector, is also involved in stress fiber formation downstream of Rho activation (11), possibly by regulating actin polymerization and focal adhesion turnover through its association with profilin (12, 13) and src-tyrosine-kinase (14), respectively.Cyclic uniaxial stretch induces the orientation of stress fibers in endothelial cells ...

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Profilins as regulators of actin dynamics

Cited by 186 publications

References 130 publications

Fine-tuning of neuronal architecture requires two profilin isoforms

Fine-tuning of neuronal architecture requires two profilin isoforms

Pollen Profilin Function Depends on Interaction with Proline-Rich Motifs

Cooperative effects of Rho and mechanical stretch on stress fiber organization

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