Mapmodulin/Leucine-rich Acidic Nuclear Protein Binds the Light Chain of Microtubule-associated Protein 1B and Modulates Neuritogenesis

Opal, Puneet; Garcı́a, Jesús; Propst, Friedrich; Matilla, Antoni; Orr, Harry T.; Zoghbi, Huda Y.

doi:10.1074/jbc.m302785200

Cited by 63 publications

(64 citation statements)

References 73 publications

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“…In addition, several studies have shown that pp32 is involved in "histone masking," which can lead to inhibition of histone acetyltransferase-dependent transcriptional activation (19,33,56). We have previously shown that the I 1 PP2A colocalizes with neurofibrillary pathology and that the transcription of I 1 PP2A is up-regulated in the affected areas of AD brain, and I 1 PP2A is, thus, a primary suspect in Alzheimer neurofibrillary degeneration (26).…”

Section: Pp2amentioning

confidence: 99%

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

Chen

Grundke‐Iqbal

et al. 2008

Journal of Biological Chemistry

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In Alzheimer disease (AD) brain, the level of I 1 PP2A, a 249-amino acid long endogenous inhibitor of protein phosphatase 2A (PP2A), is increased, the activity of the phosphatase is decreased, and the microtubule-associated protein Tau is abnormally hyperphosphorylated. However, little is known about the detailed regulatory mechanism by which PP2A activity is inhibited by I 1 PP2A and the consequent events in mammalian cells. In this study, we found that both I 1 PP2A and its N-terminal half I 1 PP2A(1-120), but neither I 1 PP2A(1-163) nor I 1 PP2A(164 -249) , inhibited PP2A activity in vitro, suggesting an autoinhibition by amino acid residues 121-163 and its neutralization by the C-terminal region. Furthermore, transfection of NIH3T3 cells produced a dose-dependent inhibition of PP2A activity by I 1 PP2A . I 1 PP2A and PP2A were found to colocalize in PC12 cells. I 1 PP2A could only interact with the catalytic subunit of PP2A (PP2Ac) and had no interaction with the regulatory subunits of PP2A (PP2A-A or PP2A-B) using a glutathione S-transferase-pulldown assay. The interaction was further confirmed by coimmunoprecipitation of I 1 PP2A and PP2Ac from lysates of transiently transfected NIH3T3 cells. The N-terminal isotype specific region of I 1 PP2A was required for its association with PP2Ac as well as PP2A inhibition. In addition, the phosphorylation of Tau was significantly increased in PC12/Tau441 cells transiently transfected with full-length I 1 PP2A and with PP2Ac-interacting I 1 PP2A deletion mutant 1-120 (I 1 PP2A ⌬C2). Double immunofluorescence staining showed that I 1 PP2A and I 1 PP2A ⌬C2 increased Tau phosphorylation and impaired the microtubule network and neurite outgrowth in PC12 cells treated with nerve growth factor.

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Section: Pp2amentioning

confidence: 99%

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

Chen

Grundke‐Iqbal

et al. 2008

Journal of Biological Chemistry

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“…In this location, these proteins were postulated to play a role in signal transduction (37). In the cytoplasm, LANP binds to all classes of structural microtubuleassociated proteins (MAPs) (11,27,35,36). No other protein, besides tubulin, shares such an extensive repertoire of MAP binding capacity.…”

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confidence: 99%

“…The C-terminal domain, on the other hand, is extended and hydrophilic, engaging interactors by virtue of its ionic interactions (23,27,30,31).…”

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confidence: 99%

Generation and Characterization of LANP/pp32 Null Mice

Opal

Garcı́a

McCall

et al. 2004

Molecular and Cellular Biology

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The leucine-rich acidic nuclear protein (LANP) belongs to a family of evolutionarily conserved proteins that are characterized by an amino-terminal domain rich in leucine residues followed by a carboxy-terminal acidic tail. LANP has been implicated in the regulation of a variety of cellular processes including RNA transport, transcription, apoptosis, vesicular trafficking, and intracellular signaling. Abundantly expressed in the developing cerebellum, this protein has also been hypothesized to play a role in cerebellar morphogenesis. LANP has been implicated in disease biology as well, both as a mediator of toxicity in spinocerebellar ataxia type 1 and as a tumor suppressor in cancers of the breast and prostate. To better understand the function of this multifaceted protein, we have generated mice lacking LANP. Surprisingly, these mice are viable and fertile. In addition we could not discern any derangements in any of the major organ systems, including the nervous system, which we have studied in detail. Overall our results point to a functional redundancy of LANP's function, most likely provided by its closely related family members.Leucine-rich acidic nuclear protein (LANP or pp32 [for phosphoprotein with a molecular mass of 32 kDa]) is a member of the leucine-rich family of proteins (16-18). These proteins are involved in a variety of pathways including signaling, protein degradation, cytoskeletal dynamics, and morphogenesis, presumably based on the ability of the leucine-rich repeat (LRR) domains to serve as adapter sites for protein-protein interactions.For LANP, the hydrophobic LRRs reside in its N-terminal domain, giving LANP a globular head domain. The C-terminal domain, on the other hand, is extended and hydrophilic, engaging interactors by virtue of its ionic interactions (23,27,30,31).Several proteins have extensive homology to LANP, both in displaying LRRs in their N terminal domains and in demonstrating extended acidic tail domains. These proteins represent true LANP family members that have probably arisen by gene duplication. The nomenclature of LANP family members is confusing because the same protein has been given more than one name based on the context of isolation. Thus APRIL, an acronym derived from A protein rich in leucines, is also known as PAL-31, for proliferation-associated leucine-rich protein, MW 31kDa, and SSP-29, for silver-stainable protein with a molecular mass of 29 kDa (24,25,41). CPD1 (cerebellar postnatal development protein 1), another LANP family member, has been called LANP-like protein (LANP-L) (21, 28). Two human homologues of LANP/pp32 have been called pp32r1 and pp32r2 to signify that they are related (14,15). Besides having homology with these proteins, LANP family members also have limited homology to template-activating factor (TAF) proteins, TAF-1 alpha and beta (the latter being the product of the SET oncogene). The TAF-1 proteins, like the LANP family members, demonstrate long acidic C-terminal domains but, unlike LANP, do not display LRRs in their Nterminal doma...

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“…It is widely believed that MAP1B could act as a scaffold for many of the above mentioned factors by anchoring them to the MT cytoskeleton or controlling their activity and localization. MAP1B has been linked to various neurodegenerative disorders, including Parkinson's disease (Chan et al 2014;Jensen et al 2000), Alzheimer's disease (Gevorkian et al 2008;Good et al 2004;Hasegawa et al 1990), giant axonal neuropathy (Allen et al 2005;Ding et al 2002), spinocerebellar ataxia type 1 (Opal et al 2003), fragile X syndrome (Brown et al 2001;Lu et al 2004;Zalfa et al 2003), and the eye-related muscular disorder congenital fibrosis of the extraocular muscles type 1 (CFEOM) (Cheng et al 2014). …”

Section: Map1 Family Member Map1bmentioning

confidence: 99%

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

2016

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Dendrites have a unique microtubule organization. In vertebrates, dendritic microtubules are organized in antiparallel bundles, oriented with their plus ends either pointing away or toward the soma. The mixed microtubule arrays control intracellular trafficking and local signaling pathways, and are essential for dendrite development and function. The organization of microtubule arrays largely depends on the combined function of different microtubule regulatory factors or generally named microtubule-associated proteins (MAPs). Classical MAPs, also called structural MAPs, were identified more than 20 years ago based on their ability to bind to and copurify with microtubules. Most classical MAPs bind along the microtubule lattice and regulate microtubule polymerization, bundling, and stabilization. Recent evidences suggest that classical MAPs also guide motor protein transport, interact with the actin cytoskeleton, and act in various neuronal signaling networks. Here, we give an overview of microtubule organization in dendrites and the role of classical MAPs in dendrite development, dendritic spine formation, and synaptic plasticity. IntroductionMicrotubules (MTs) are cytoskeletal structures that play essential roles in all eukaryotic cells. MTs are important not only during cell division but also in non-dividing cells, where they are critical structures in numerous cellular processes such as cell motility, migration, differentiation, intracellular transport and organelle positioning. MTs are composed of two proteins, α-and β-tubulin, that form heterodimers and organize themselves in a head-to-tail manner. MTs are dynamic and they can rapidly switch between cycles of growth and shrinkage. This MT

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Mapmodulin/Leucine-rich Acidic Nuclear Protein Binds the Light Chain of Microtubule-associated Protein 1B and Modulates Neuritogenesis

Cited by 63 publications

References 73 publications

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

Generation and Characterization of LANP/pp32 Null Mice

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

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