ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
The role of microtubule-associated protein 2c in the reorganization of microtubules and lamellipodia during neurite initiation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 170 citations in OpenAlex.
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- Temporal Quantitative Proteomic and Phosphoproteomic Profiling of SH-SY5Y and IMR-32 Neuroblastoma Cells during All-International journal of molecular sciences · 2024Article
- Differential regulation of MAP2 by phosphorylation events in proline-rich versus C-terminal domains.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation.Current biology : CB · 2023Article
- Establishing neuronal polarity: microtubule regulation during neurite initiation.Oxford open neuroscience · 2022Review
- More than a marker: potential pathogenic functions of MAP2.Frontiers in molecular neuroscience · 2022Article
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- SUMOylation of α-tubulin is a novel modification regulating microtubule dynamics.Journal of molecular cell biology · 2021Article
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- P-Rex1 Overexpression Results in Aberrant Neuronal Polarity and Psychosis-Related Behaviors.Neuroscience bulletin · 2019Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
During neurite initiation, cells surrounded by a flattened, actin-rich lamellipodium transform to produce thin, microtubule-filled neurite shafts tipped by actin-rich growth cones, but little is known about this transformation. Our detailed time-lapse analyses of cultured hippocampal neurons, a widely used model system for neuronal development, revealed that neurites emerge from segmented lamellipodia, which then gradually extend from the cell body to become nascent growth cones. This suggests that actin- and microtubule-rich structures are reorganized in a coordinated manner. We hypothesized that proteins such as microtubule-associated protein 2 (MAP2), which can interact with both cytoskeletal components, might be critically involved in neurite initiation. Live-cell video and fluorescence microscopy in Neuro-2a cells showed that expression of MAP2c triggers neurite formation via rapid accumulation and bundling of stable, MAP2c-bound microtubules, concurrent with a gradual transformation of lamellipodia into nascent growth cones. The microtubule-stabilizing agent Taxol did not mimic this effect, suggesting that the ability of MAP2c to stabilize microtubules is not sufficient for neurite initiation. However, combination of Taxol treatment with actin disruption induced robust process formation, suggesting that inhibitory effects of F-actin need to be overcome as well. Neurite initiation by MAP2c required its microtubule-binding domain and was enhanced by its binding domain for cAMP-dependent protein kinase (PKA). MAP2c mutants defective in both PKA and microtubule binding acted as dominant negative inhibitors of neurite initiation in neuroblastoma cells and primary hippocampal neurons. Together, these data suggest that MAP2c bears functions that both stabilize microtubules and directly or indirectly alter actin organization during neurite initiation.
Indexed as
Identifiers
14573527PMC6740480W1893566722What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.