Role of vimentin in early stages of neuritogenesis in cultured hippocampal neurons

Boyne, Lesley J.; Fischer, Itzhak; Shea, Thomas B.

doi:10.1016/s0736-5748(96)00053-6

Cited by 60 publications

(54 citation statements)

References 60 publications

(6 reference statements)

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“…Indeed, morphologically, Ndel1-depleted CAD cells mimicked the outgrowth defects observed in neurons and neuroblastoma cell lines lacking vimentin (23,24,27). However, we found no difference in levels of vimentin in Ndel1-RNAi-treated cells when compared with control cells (Fig.…”

Section: Formation Of the Novel Ndel1 Complex In Neuronal Cellssupporting

confidence: 56%

“…Based on our biochemical data, we hypothesized that Ndel1 affects vimentin, which is critical for neurite extension in neu- roblastoma cells and primary cultured neurons (23,24,27). Indeed, morphologically, Ndel1-depleted CAD cells mimicked the outgrowth defects observed in neurons and neuroblastoma cell lines lacking vimentin (23,24,27).…”

Section: Formation Of the Novel Ndel1 Complex In Neuronal Cellsmentioning

confidence: 87%

“…4 and 5). Indeed, depletion of Ndel1 by RNAi impairs vimentin dynamics (which is critical for vimentin assembly and functions), resulting in neurite outgrowth defects reminiscent of those exhibited by cells depleted of vimentin (23,24,27). Previously, Ndel1 together with DISC1 have been shown to be important for neurite outgrowth in PC-12 cells (2).…”

Section: A Novel Ndel1 Molecular Complex During Neurite Outgrowth-mentioning

confidence: 99%

“…Ndel1 also interacts with the Disrupted-in-Schizophrenia protein 1 (DISC1) to regulate MT dynamics during neurite outgrowth in neuroblastoma PC-12 cells and during neuronal migration in the developing cortex. Interestingly, Ndel1 associates with the molecular motors dynein/dynactin (20 -22), and numerous independent reports documented the dynein transport of the vimentin, an IF important for glial activation and neurite formation and exhibiting pro-and anti-regenerative properties following axonal injury (13)(14)(15)(16)(23)(24)(25)(26)(27)(28)(29). Whether Ndel1 associates with the dynein-vimentin complex during neurite outgrowth and regulates vimentin dynamics remains elusive.…”

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confidence: 99%

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Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth

Shim

Samuels

Wang

et al. 2008

Journal of Biological Chemistry

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Ndel1, the mammalian homologue of the Aspergillus nidulans NudE, is emergently viewed as an integrator of the cytoskeleton. By regulating the dynamics of microtubules and assembly of neuronal intermediate filaments (IFs), Ndel1 promotes neurite outgrowth, neuronal migration, and cell integrity (1-6). To further understand the roles of Ndel1 in cytoskeletal dynamics, we performed a tandem affinity purification of Ndel1-interacting proteins. We isolated a novel Ndel1 molecular complex composed of the IF vimentin, the molecular motor dynein, the lissencephaly protein Lis1, and the cis-Golgi-associated protein ␣COP. Ndel1 promotes the interaction between Lis1, ␣COP, and the vimentin-dynein complex. The functional result of this complex is activation of dynein-mediated transport of vimentin. A loss of Ndel1 functions by RNA interference fails to incorporate Lis1/␣COP in the complex, reduces the transport of vimentin, and culminates in IF accumulations and altered neuritogenesis. Our findings reveal a novel regulatory mechanism of vimentin transport during neurite extension that may have implications in diseases featuring transport/trafficking defects and impaired regeneration.The cytoskeleton constitutes a highly organized structure formed by the interconnection of three filamentous networks (microtubules (MTs), 3 intermediate filaments (IFs), and microfilament) and their associated proteins (7-10). The dynamics of these networks regulate essential intracellular functions such as transport and trafficking and, therefore, impact on cell division, morphology, and integrity (7-10). Named according to their intermediate diameter (10 nm), IFs constitute the largest family of cytoskeletal proteins. Up to 60 genes encoding for IFs are expressed in a tissue-specific and spatio-temporal manner in mammals (7,11,12). After synthesis in the cytoplasm, a fraction of soluble IF proteins is rapidly incorporated into the polymeric filamentous network, referred to as the "insoluble" fraction (7, 12). In parallel, individual IF subunits, dimers, or small oligomers that constitute the "soluble" fraction translocate rapidly along MTs via molecular motors in structures termed particles (13,14). This model is particularly relevant for the assembly of the IF vimentin (15, 16) and more controversial in the case of neuronal IFs (NFs) (17-19).The neurofilament proteins (NF-L, NF-M, and NF-H) are the most abundant IFs in mature central nervous system neurons (12). We recently demonstrated that Ndel1, the mammalian homologue of the Aspergillus nidulans NudE, a protein implicated in nuclear distribution during hyphal growth, binds directly to the key subunit NF-L, thereby regulating NF assembly (5). Ndel1 also interacts with the Disrupted-in-Schizophrenia protein 1 (DISC1) to regulate MT dynamics during neurite outgrowth in neuroblastoma PC-12 cells and during neuronal migration in the developing cortex. Interestingly, Ndel1 associates with the molecular motors dynein/dynactin (20 -22), and numerous independent reports documented the dynein tran...

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Section: Formation Of the Novel Ndel1 Complex In Neuronal Cellssupporting

confidence: 56%

Section: Formation Of the Novel Ndel1 Complex In Neuronal Cellsmentioning

confidence: 87%

Section: A Novel Ndel1 Molecular Complex During Neurite Outgrowth-mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth

Shim

Samuels

Wang

et al. 2008

Journal of Biological Chemistry

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“…Vimentin is prominent within newly-elaborated axons in situ and in culture [Cochard and Paulin, 1984;Jacobs et al, 1982;Tapscott et al, 1981] and facilitates the development of neuronal polarity [Boyne et al, 1996;Shea, 1990;Shea et al, 1993a]. The neuronal intermediate filament ␣-internexin [Fliegner et al, 1990;Chiu et al, 1989] apparently does not function in axonal initiation, but instead supports elongation of newly-elaborated axonal neurites [Shea and Beermann, 1999].…”

Section: Introductionmentioning

confidence: 99%

Selective accumulation of the high molecular weight neurofilament subunit within the distal region of growing axonal neurites

Yabe

Wang

Chylinski

et al. 2001

Cell Motil. Cytoskeleton

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Axonal maturation in situ is accompanied by the transition of neurofilaments (NFs) comprised of only NF-M and NF-L to those also containing NF-H. Since NF-H participates in interactions of NFs with each other and with other cytoskeletal constituents, its appearance represents a critical event in the stabilization of axons that accompanies their maturation. Whether this transition is effected by replacement of "doublet" NFs with "triplet" NFs, or by incorporation of NF-H into existing doublet NFs is unclear. To address this issue, we examined the distribution of NF subunit immunoreactivity within axonal cytoskeletons of differentiated NB2a/d1 cell and DRG neurons between days 3-7 of outgrowth. Endogenous immunoreactivity either declined in a proximal-distal gradient or was relatively uniform along axons. This distribution was paralleled by microinjected biotinylated NF-L. By contrast, biotinylated NF-H displayed a bipolar distribution, with immunoreactivity concentrated within the proximal- and distal-most axonal regions. Proximal biotinylated NF-H accumulation paralleled that of endogenous NF immunoreactivity; however, distal-most biotinylated NF-H accumulation dramatically exceeded that of endogenous NFs and microinjected NF-L. This phenomenon was not due to co-polymerization of biotin-H with vimentin or alpha-internexin. This phenomenon declined with continued time in culture. These data suggest that NF-H can incorporate into existing cytoskeletal structures, and therefore suggest that this mechanism accounts for at least a portion of the accumulation of triplet NFs during axonal maturation. Selective NF-H accumulation into existing cytoskeletal structures within the distal-most region may provide de novo cytoskeletal stability for continued axon extension and/or stabilization.

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Neuronal intermediate filament protein ?-internexin facilitates axonal neurite elongation in neuroblastoma cells

Shea

Beermann

1999

Cell Motil. Cytoskeleton

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We examined the localization and role of α‐IN vs. other neuronal intermediate filaments before and during differentiation. Vimentin but not α‐IN localized within filopodia‐like neurites of undifferentiated cells. During differentiation, α‐IN immunoreactivity accumulated within axonal neurites following vimentin but, as previously describe in neurons in situ, before the appearance of NF‐L. We therefore manipulated α‐IN synthesis, accumulation, and function in attempts to determine whether or not this intermediate filament species played a role in axonal development. Intracellular delivery of anti‐α‐IN antisense oligonucleotides and antibodies was permissive for neuritogenesis, yet compromised neurite elongation; this effect was further reflected in diminished levels of stabilized axonal microtubules. These data suggest that α‐IN plays a role in the development of neuronal polarity. Relatively more α‐IN than NF‐L accumulated within the plastic axonal neurites induced following serum‐deprivation, while stable, dbcAMP‐induced neurites treatment contained equivalent levels of each. Protease inhibition increased NF‐L and NF‐H but not α‐IN immunoreactivity within serum‐deprived neurites, suggesting that proteolysis restricts NF‐L accumulation pending neurite stabilization. To test the possibility that NF‐H accumulation is dependent upon NF‐L and cannot be mediated by α‐IN, we examined levels of NF‐H co‐precipitated from cells with α‐IN and NF‐L. Virtually all newly synthesized NF‐H co‐precipitated with NF‐L, while only a small percentage co‐precipitated with α‐IN. Finally, NF‐H or NF‐M were absent from the axon hillock or perikaryal area at the base of neurites, where α‐IN immunoreactivity is prominent. These data extend earlier cell‐free demonstrations that NF‐H preferentially associates with NF‐L rather than α‐IN. Cell Motil. Cytoskeleton 43:322–333, 1999. © 1999 Wiley‐Liss, Inc.

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Role of vimentin in early stages of neuritogenesis in cultured hippocampal neurons

Cited by 60 publications

References 60 publications

Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth

Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth

Selective accumulation of the high molecular weight neurofilament subunit within the distal region of growing axonal neurites

Neuronal intermediate filament protein ?-internexin facilitates axonal neurite elongation in neuroblastoma cells

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