Disease relevance of EPB41L1

• Immunofluorescence studies show that protein 4.1N and D2 and D3 dopamine receptors are expressed at the plasma membrane of transfected human embryonic kidney 293 and mouse neuroblastoma Neuro2A cells [1].

High impact information on EPB41L1

• C-terminal palmitoylation decreases interaction of the AMPA receptor with the 4.1N protein and regulates AMPA- and NMDA-induced AMPA receptor internalization [2].
• Association of the type 1 inositol (1,4,5)-trisphosphate receptor with 4.1N protein in neurons [3].
• From our findings we hypothesize that InsP(3)R1-4.1N association may play a role in InsP(3)R1 localization or Ca(2+) signaling in neurons [3].
• In yeast two-hybrid screen of rat brain cDNA library with the InsP(3)R1 carboxy-terminal bait we isolated multiple clones of neuronal cytoskeletal protein 4.1N [3].
• We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes [3].

Biological context of EPB41L1

• Radiation hybrid mapping of EPB41L1, a novel protein 4.1 homologue, to human chromosome 20q11.2-q12 [4].
• Thus, nuclear 4.1N appears to mediate the antiproliferative actions of NGF by antagonizing the role of NuMA in mitosis [5].
• Specific targeting of 4.1N to the nucleus arrests PC12 cells at the G1 phase and produces an aberrant nuclear morphology [5].
• Inhibition of 4.1N nuclear translocation prevents the NGF-mediated arrest of cell division, which can be reversed by overexpression of 4.1N [5].

Anatomical context of EPB41L1

• These results suggest that protein 4.1N may link AMPA receptors to the actin cytoskeleton [6].
• These results suggest that protein 4.1N/dopamine receptor interaction is required for localization or stability of dopamine receptors at the neuronal plasma membrane [1].
• Protein 4.1N is a neuronal selective isoform of the erythrocyte membrane cytoskeleton protein 4.1R [5].
• 4.1G mRNA is highly expressed in brain, spinal cord and testis; 4.1N in brain, spinal cord and adrenal gland; 4.1B in testis, brain, spinal cord, and kidney [7].

Associations of EPB41L1 with chemical compounds

• We identified protein 4.1N as a D2-like dopamine receptor-interacting protein in a yeast two-hybrid screen [1].
• Using comparative immunoblot analysis, we found that treatment with either haloperidol or clozapine increased D2 dopamine receptors, calcium activator protein for secretion, protein 4.1N, and neuronal calcium sensor-1 expression [8].

Physical interactions of EPB41L1

• Protein 4.1N binding to nuclear mitotic apparatus protein in PC12 cells mediates the antiproliferative actions of nerve growth factor [5].

Other interactions of EPB41L1

• We also found that 4.1N can associate with GluR1 in vivo and colocalizes with AMPA receptors at excitatory synapses [6].
• Thus, 4.1N, 4.1B and 4.1G all show high accumulation in nervous tissues. mRNA for betaIISigma2-spectrin is ubiquitous, but most abundant in cardiac and nervous tissues [7].

References