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Association of HAP1 Isoforms with a Unique Cytoplasmic Structure
Author(s) -
Li ShiHua,
Gutekunst ClaireAnne,
Hersch Steven M.,
Li XiaoJiang
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71052178.x
Subject(s) - gene isoform , biology , cytoplasm , complementary dna , microbiology and biotechnology , transfection , cell culture , biochemistry , genetics , gene
HAP1 is a neural protein and interacts with the Huntington's disease protein huntingtin. There are at least two HAP1 isoforms, HAP1‐A and HAP1‐B, which have different C‐terminal amino acid sequences. Here we report that both HAP1 isoforms associate with a unique cytoplasmic structure in neurons of rat brain. The HAP1‐immunoreactive structure appears as an inclusion that is an oval mass of electron‐dense material, 0.5–3 µm in diameter, containing many curvilinear or ring‐shaped segments, and often containing electron‐lucent cores. This structure is very similar to those previously termed the stigmoid body, nematosome, or botrysome. Transfection of cell lines with cDNA encoding HAP1‐A, but not HAP1‐B, resulted in similar HAP1‐immunoreactive inclusions in the cytoplasm, suggesting that HAP1‐A is essential to the formation of this structure. Yeast two‐hybrid and transfection studies show that both HAP1‐A and HAP1‐B can self‐associate, implying that native HAP1 in the cytoplasmic inclusion may be a heteromultimer of HAP1‐A and HAP1‐B. Coexpression of HAP1‐A and HAP1‐B in human embryonic kidney 293 cells demonstrates that the ratio of the expressed HAP1‐A to HAP1‐B regulates the formation of HAP1‐associated inclusions. We propose that HAP1 isoforms are involved in the formation of HAP1‐immunoreactive inclusions in the neuronal cytoplasm.