The expression of Huntingtin‐associated protein (HAP1) mRNA in developing, adult and ageing rat CNS: implications for Huntington's disease neuropathology

Page, Kyle S.; Potter, Laurence; Aronni, Silvia; Everitt, Barry J.; Dunnett, Stephen B.

doi:10.1046/j.1460-9568.1998.00185.x

Cited by 45 publications

(50 citation statements)

References 35 publications

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“…Previous studies on HAP1 were mainly concentrated on its relations to HD pathology and its role in neurons. The early biochemical, in situ hybridization histochemical, and immunohistochemical studies on HAP1 expression and distribution have indicated that HAP1 is a brain-specific protein, though its expression in reproductive glands and pituitary gland is also detected by in situ hybridization histochemistry (Li et al 1995(Li et al ,1996Gutekunst et al 1998;Page et al 1998;Dragatsis et al 2000;Fujinaga et al 2004). The present immunohistochemical study shows for the first time that HAP1 is present in the following endocrine organs or tissues: pituitary, thyroid, adrenal medulla, pancreas islet, and mucosa of gastrointestinal tract.…”

Section: Discussionsupporting

confidence: 47%

Immunohistochemical Localization of Huntingtin-associated Protein 1 in Endocrine System of the Rat

Liu

Shen

Zhang

et al. 2005

J Histochem Cytochem.

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S U M M A R YHuntingtin-associated protein 1 (HAP1) was originally found to be localized in neurons and is thought to play an important role in neuronal vesicular trafficking and/or organelle transport. Based on functional similarity between neuron and endocrine cell in vesicular trafficking, we examined the expression and localization of HAP1 in the rat endocrine system using immunohistochemistry. HAP1-immunoreactive cells are widely distributed in the anterior lobe of the pituitary, scattered in the wall of the thyroid follicles, or clustered in the interfollicular space of the thyroid gland, exclusively but diffusely distributed in the medullae of adrenal glands, and selectively located in the pancreas islets. HAP1-containing cells were also found in the mucosa of stomach and small intestine with a distributive pattern similar to that of gastrointestinal endocrine cells. However, no HAP1-immunoreactive cell was found in the cortex of the adrenal gland, the testis, and the ovary. In the posterior lobe of the pituitary, HAP1-immunoreactive products were not detected in the cell bodies but in many stigmoid bodies, one kind of non-membrane-bound cytoplasmic organelle with a central or eccentric electron-lucent core. HAP1-immunoreactive stigmoid bodies were also found in the cytoplasm of endocrine cells in the thyroid gland, the medullae of adrenal gland, the pancreas islets, the stomach, and small intestine. The present study demonstrates that HAP1 is selectively expressed in part of the small peptide-, protein-, and amino-acid analog and derivative-secreting endocrine cells but not in steroid hormone-secreting cells, suggesting that HAP1 is also involved in intracellular trafficking in certain types of endocrine cells.

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Section: Discussionsupporting

confidence: 47%

Immunohistochemical Localization of Huntingtin-associated Protein 1 in Endocrine System of the Rat

Liu

Shen

Zhang

et al. 2005

J Histochem Cytochem.

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“…Consistent with its potential involvement in neuropathology, Hap1 is enriched in neuronal cells (6). However, the expression of Hap1 in mouse brain is developmentally regulated (7,8) and varies in different regions, with the highest level in the hypothalamus that is regulated by feeding behavior (9). Thus, Hap1's function may be cell-type dependent and is critical for hypothalamic function, which regulates the growth and energy balance of animals.…”

Section: Introductionmentioning

confidence: 96%

Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin receptor sorting

Xiang¹,

Yang²,

Zhao³

et al. 2013

J. Clin. Invest.

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Defective neurogenesis in the postnatal brain can lead to many neurological and psychiatric disorders, yet the mechanism behind postnatal neurogenesis remains to be investigated. Huntingtin-associated protein 1 (HAP1) participates in intracellular trafficking in neurons, and its absence leads to postnatal death in mice. Here, we used tamoxifen-induced (TM-induced) Cre recombination to deplete HAP1 in mice at different ages. We found that HAP1 reduction selectively affects survival and growth of postnatal mice, but not adults. Neurogenesis, but not gliogenesis, was affected in HAP1-null neurospheres and mouse brain. In the absence of HAP1, postnatal hypothalamic neurons exhibited reduced receptor tropomyosin-related kinase B (TRKB) levels and decreased survival. HAP1 stabilized the association of TRKB with the intracellular sorting protein sortilin, prevented TRKB degradation, and promoted its anterograde transport. Our findings indicate that intracellular sorting of neurotrophin receptors is critical for postnatal neurogenesis and could provide a therapeutic target for defective postnatal neurogenesis.

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“…In contrast, little expression of HAP1 is detected in the striatum and thalamus (Li et al 1995(Li et al ,1996Page et al 1998;Gutekunst et al 1998;Martin et al 1999). Then, Dragatsis et al (2000) studied the HAP1 gene expression in developing and adult mice by Northern blotting and ISH, and detected HAP1 mRNA not only in the nervous system but also in the reproductive system and pituitary glands (Dragatsis et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Selective Expression of Huntingtin-associated Protein 1 in β-Cells of the Rat Pancreatic Islets

Liu

Chen

Han

et al. 2009

J Histochem Cytochem.

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(ML) S U M M A R Y Huntingtin-associated protein-1 (HAP1) was initially identified as a binding partner of huntingtin, the Huntington's disease protein. Based on its preferred distribution among neurons and endocrine cells, HAP1 has been suggested to play roles in vesicular transportation in neurons and hormonal secretion of endocrine cells. Given that HAP1 is selectively expressed in the islets of rat pancreas, in this study, we analyzed the expression pattern of HAP1 in the islets. In rats injected intraperitoneally with streptozotocin, which can selectively destroy b-cells of the pancreatic islets, the number of HAP1 immunoreactive cells was dramatically decreased and was accompanied by a parallel decrease in the number of insulin-immunoreactive cells. Immunofluorescent double staining of pancreas sections showed that, in rat islets, HAP1 is selectively expressed in the insulin-immunoreactive b-cells but not in the glucagon-immunoreactive a-cells and somatostatin immunoreactive y-cells. In isolated rat pancreatic islets, ?80% of cells expressed both HAP1 and insulin. Expression of HAP1 in the INS-1 rat insulinoma cell line was also demonstrated by immunofluorescent staining. Western blotting further revealed that HAP1 in both the isolated rat pancreatic islets and the INS-1 cells also has two isoforms, HAP1A and HAP1B, which are the same as those in the hypothalamus. These results demonstrated that HAP1 is selectively expressed in b-cells of rat pancreatic islets, suggesting the involvement of HAP1 in the regulation of cellular trafficking and secretion of insulin. (J Histochem Cytochem 58:255-263, 2010)

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The expression of Huntingtin‐associated protein (HAP1) mRNA in developing, adult and ageing rat CNS: implications for Huntington's disease neuropathology

Cited by 45 publications

References 35 publications

Immunohistochemical Localization of Huntingtin-associated Protein 1 in Endocrine System of the Rat

Immunohistochemical Localization of Huntingtin-associated Protein 1 in Endocrine System of the Rat

Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin receptor sorting

Selective Expression of Huntingtin-associated Protein 1 in β-Cells of the Rat Pancreatic Islets

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