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Interaction of Tubby-Like Protein-1 (Tulp1) and Microtubule-Associated Protein (MAP) 1A and MAP1B in the Mouse Retina

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Tubby-like protein-1 (Tulp1) is a photoreceptor-specific protein involved in the transport of specific proteins from the inner segment (IS) to the outer segment (OS) in photoreceptor cells. Mutations in the human TULP1 gene cause an early onset form of retinitis pigmentosa. Our previous work has shown an association between Tulp1 and the microtubule-associated protein, MAP1B. An allele of Mtap1a, which encodes the MAP1A protein, significantly delays photoreceptor degeneration in Tulp1 mutant mice. MAP1 proteins are important in stabilizing microtubules in neuronal cells, but their role in photoreceptors remains obscure. To investigate the relationship between Tulp1 and MAP1 proteins, we performed western blots, immunoprecipitations (IP), immunohistochemistry and proximity ligand assays (PLA) in wild-type and tulp1−/− mouse retinas. Our IP experiments provide evidence that Tulp1 and MAP1B interact while PLA experiments localize their interaction to the outer nuclear layer and IS of photoreceptors. Although MAP1A and MAP1B protein levels are not affected in the tulp1−/− retina, they are no longer localized to the OS of photoreceptors. This may be the cause for disorganized OSs in tulp1−/− mice, and indicate that their transport to the OS is Tulp1-dependent.

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Abbreviations

BS3 :

Bis[sulfosuccinimidyl] suberate

CC:

Connecting cilium

GCL:

Ganglion cell layer

IFT:

Intraflagellar transport

IHC:

Immunohistochemistry

INL:

Inner nuclear layer

IP:

Immunoprecipitations

IPL:

Inner plexiform layer

IS:

Inner segment

MAP:

Microtubule-associated protein

MW:

Molecular weight

ONL:

Outer nuclear layer

OPL:

Outer plexiform layer

OS:

Outer segment

P:

Postnatal day

PFA:

Paraformaldehyde

PLA:

Proximity ligand assays

RP1:

Retinitis pigmentosa 1 protein

SDS:

Sodium dodecyl sulfate

Tulp1:

Tubby-like protein-1

WB:

Western blot

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Acknowledgments

This study was supported by NIH Grant EY15638 (SAH), a Research to Prevent Blindness Center Grant and a Knights Templar Pediatric Ophthalmology Career-Starter Research Grant (GHG).

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Authors and Affiliations

  1. Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA

    Gregory H. Grossman, Craig D. Beight, Lindsey A. Ebke, Gayle J.T Pauer & Stephanie A. Hagstrom

  2. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 44195, Cleveland, OH, USA

    Stephanie A. Hagstrom

Authors
  1. Gregory H. Grossman
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  2. Craig D. Beight
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  3. Lindsey A. Ebke
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  4. Gayle J.T Pauer
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  5. Stephanie A. Hagstrom
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Corresponding author

Correspondence to Stephanie A. Hagstrom .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Grossman, G., Beight, C., Ebke, L., Pauer, G., Hagstrom, S. (2014). Interaction of Tubby-Like Protein-1 (Tulp1) and Microtubule-Associated Protein (MAP) 1A and MAP1B in the Mouse Retina. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_65

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_65

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

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