A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1

Loren D. Walensky, Seth Blackshaw, Dezhi Liao, Crystal Watkins, Heinz Ulrich G Weier, Marilyn Parra, Richard L Huganir, John G. Conboy, Narla Mohandas, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

We report the molecular cloning and characterization of 4.1N, a novel neuronal homolog of the erythrocyte membrane cytoskeletal protein 4.1 (4.1R). The 879 amino acid protein shares 70, 36, and 46% identity with 4.1R in the defined membrane-binding, spectrin-actin-binding, and C-terminal domains, respectively. 4.1N is expressed in almost all central and peripheral neurons of the body and is detected in embryonic neurons at the earliest stage of postmitotic differentiation. Like 4.1R, 4.1N has multiple splice forms as evidenced by PCR and Western analysis. Whereas the predominant 4.1N isoform identified in brain is ~135 kDa, a smaller 100 kDa isoform is enriched in peripheral tissues. Immunohistochemical studies using a polyclonal 4.1N antibody revealed several patterns of neuronal staining, with localizations in the neuronal cell body, dendrites, and axons. In certain neuronal locations, including the granule cell layers of the cerebellum and dentate gyrus, a distinct punctate-staining pattern was observed consistent with a synaptic localization. In primary hippocampal cultures, mouse 4.1N is enriched at the discrete sites of synaptic contact, colocalizing with the postsynaptic density protein of 95 kDa (a postsynaptic marker) and glutamate receptor type 1 (an excitatory postsynaptic marker). By analogy with the roles of 4.1R in red blood cells, 4.1N may function to confer stability and plasticity to the neuronal membrane via interactions with multiple binding partners, including the spectrin-actin-based cytoskeleton, integral membrane channels and receptors, and membrane-associated guanylate kinases.

Original languageEnglish (US)
Pages (from-to)6457-6467
Number of pages11
JournalJournal of Neuroscience
Volume19
Issue number15
StatePublished - Aug 1 1999

Fingerprint

Spectrin
Cytoskeletal Proteins
Erythrocyte Membrane
Protein Isoforms
Membrane Proteins
Guanylate Kinases
Staining and Labeling
Neurons
Neuronal Plasticity
Membranes
Sexual Partners
Dentate Gyrus
Glutamate Receptors
Molecular Cloning
Dendrites
Actin Cytoskeleton
Ion Channels
Cerebellum
Axons
Actins

Keywords

  • Ankyrin
  • Cytoskeleton synapse
  • Neuron
  • Protein 4.1
  • Red blood cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1. / Walensky, Loren D.; Blackshaw, Seth; Liao, Dezhi; Watkins, Crystal; Weier, Heinz Ulrich G; Parra, Marilyn; Huganir, Richard L; Conboy, John G.; Mohandas, Narla; Snyder, Solomon H.

In: Journal of Neuroscience, Vol. 19, No. 15, 01.08.1999, p. 6457-6467.

Research output: Contribution to journalArticle

Walensky, LD, Blackshaw, S, Liao, D, Watkins, C, Weier, HUG, Parra, M, Huganir, RL, Conboy, JG, Mohandas, N & Snyder, SH 1999, 'A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1', Journal of Neuroscience, vol. 19, no. 15, pp. 6457-6467.
Walensky, Loren D. ; Blackshaw, Seth ; Liao, Dezhi ; Watkins, Crystal ; Weier, Heinz Ulrich G ; Parra, Marilyn ; Huganir, Richard L ; Conboy, John G. ; Mohandas, Narla ; Snyder, Solomon H. / A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 15. pp. 6457-6467.
@article{47e04d7da86b4d91b8af32edadf957d8,
title = "A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1",
abstract = "We report the molecular cloning and characterization of 4.1N, a novel neuronal homolog of the erythrocyte membrane cytoskeletal protein 4.1 (4.1R). The 879 amino acid protein shares 70, 36, and 46{\%} identity with 4.1R in the defined membrane-binding, spectrin-actin-binding, and C-terminal domains, respectively. 4.1N is expressed in almost all central and peripheral neurons of the body and is detected in embryonic neurons at the earliest stage of postmitotic differentiation. Like 4.1R, 4.1N has multiple splice forms as evidenced by PCR and Western analysis. Whereas the predominant 4.1N isoform identified in brain is ~135 kDa, a smaller 100 kDa isoform is enriched in peripheral tissues. Immunohistochemical studies using a polyclonal 4.1N antibody revealed several patterns of neuronal staining, with localizations in the neuronal cell body, dendrites, and axons. In certain neuronal locations, including the granule cell layers of the cerebellum and dentate gyrus, a distinct punctate-staining pattern was observed consistent with a synaptic localization. In primary hippocampal cultures, mouse 4.1N is enriched at the discrete sites of synaptic contact, colocalizing with the postsynaptic density protein of 95 kDa (a postsynaptic marker) and glutamate receptor type 1 (an excitatory postsynaptic marker). By analogy with the roles of 4.1R in red blood cells, 4.1N may function to confer stability and plasticity to the neuronal membrane via interactions with multiple binding partners, including the spectrin-actin-based cytoskeleton, integral membrane channels and receptors, and membrane-associated guanylate kinases.",
keywords = "Ankyrin, Cytoskeleton synapse, Neuron, Protein 4.1, Red blood cell",
author = "Walensky, {Loren D.} and Seth Blackshaw and Dezhi Liao and Crystal Watkins and Weier, {Heinz Ulrich G} and Marilyn Parra and Huganir, {Richard L} and Conboy, {John G.} and Narla Mohandas and Snyder, {Solomon H}",
year = "1999",
month = "8",
day = "1",
language = "English (US)",
volume = "19",
pages = "6457--6467",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "15",

}

TY - JOUR

T1 - A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1

AU - Walensky, Loren D.

AU - Blackshaw, Seth

AU - Liao, Dezhi

AU - Watkins, Crystal

AU - Weier, Heinz Ulrich G

AU - Parra, Marilyn

AU - Huganir, Richard L

AU - Conboy, John G.

AU - Mohandas, Narla

AU - Snyder, Solomon H

PY - 1999/8/1

Y1 - 1999/8/1

N2 - We report the molecular cloning and characterization of 4.1N, a novel neuronal homolog of the erythrocyte membrane cytoskeletal protein 4.1 (4.1R). The 879 amino acid protein shares 70, 36, and 46% identity with 4.1R in the defined membrane-binding, spectrin-actin-binding, and C-terminal domains, respectively. 4.1N is expressed in almost all central and peripheral neurons of the body and is detected in embryonic neurons at the earliest stage of postmitotic differentiation. Like 4.1R, 4.1N has multiple splice forms as evidenced by PCR and Western analysis. Whereas the predominant 4.1N isoform identified in brain is ~135 kDa, a smaller 100 kDa isoform is enriched in peripheral tissues. Immunohistochemical studies using a polyclonal 4.1N antibody revealed several patterns of neuronal staining, with localizations in the neuronal cell body, dendrites, and axons. In certain neuronal locations, including the granule cell layers of the cerebellum and dentate gyrus, a distinct punctate-staining pattern was observed consistent with a synaptic localization. In primary hippocampal cultures, mouse 4.1N is enriched at the discrete sites of synaptic contact, colocalizing with the postsynaptic density protein of 95 kDa (a postsynaptic marker) and glutamate receptor type 1 (an excitatory postsynaptic marker). By analogy with the roles of 4.1R in red blood cells, 4.1N may function to confer stability and plasticity to the neuronal membrane via interactions with multiple binding partners, including the spectrin-actin-based cytoskeleton, integral membrane channels and receptors, and membrane-associated guanylate kinases.

AB - We report the molecular cloning and characterization of 4.1N, a novel neuronal homolog of the erythrocyte membrane cytoskeletal protein 4.1 (4.1R). The 879 amino acid protein shares 70, 36, and 46% identity with 4.1R in the defined membrane-binding, spectrin-actin-binding, and C-terminal domains, respectively. 4.1N is expressed in almost all central and peripheral neurons of the body and is detected in embryonic neurons at the earliest stage of postmitotic differentiation. Like 4.1R, 4.1N has multiple splice forms as evidenced by PCR and Western analysis. Whereas the predominant 4.1N isoform identified in brain is ~135 kDa, a smaller 100 kDa isoform is enriched in peripheral tissues. Immunohistochemical studies using a polyclonal 4.1N antibody revealed several patterns of neuronal staining, with localizations in the neuronal cell body, dendrites, and axons. In certain neuronal locations, including the granule cell layers of the cerebellum and dentate gyrus, a distinct punctate-staining pattern was observed consistent with a synaptic localization. In primary hippocampal cultures, mouse 4.1N is enriched at the discrete sites of synaptic contact, colocalizing with the postsynaptic density protein of 95 kDa (a postsynaptic marker) and glutamate receptor type 1 (an excitatory postsynaptic marker). By analogy with the roles of 4.1R in red blood cells, 4.1N may function to confer stability and plasticity to the neuronal membrane via interactions with multiple binding partners, including the spectrin-actin-based cytoskeleton, integral membrane channels and receptors, and membrane-associated guanylate kinases.

KW - Ankyrin

KW - Cytoskeleton synapse

KW - Neuron

KW - Protein 4.1

KW - Red blood cell

UR - http://www.scopus.com/inward/record.url?scp=0033179416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033179416&partnerID=8YFLogxK

M3 - Article

C2 - 10414974

AN - SCOPUS:0033179416

VL - 19

SP - 6457

EP - 6467

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 15

ER -