An aromatase‐associated cytoplasmic inclusion, the “stigmoid body,” in the rat brain: II. Ultrastructure (with a review of its history and nomenclature)

Abstract

The ultrastructure of aromatase-associated "stigmoid (dot-like) structures," which were detected in a previous study using light-microscopic immunohistochemistry (Shinoda et al.: J. Comp. Neurol. 322:360-376, '92), were examined in the rat medial preoptic region, bed nucleus of the stria terminalis, medial amygdaloid nucleus, and arcuate nucleus by pre- and post-embedding marking with a polyclonal antibody against human placental antigen X-P2 (hPAX-P2) for immuno-electron microscopic analysis. The immunoreactive stigmoid structure was identified as a distinct, non-membrane-bounded cytoplasmic inclusion (approximately 1-3 microns in diameter), which has a granulo-fuzzy texture with moderate-to-low electron density in non-immunostained preparations. It consists of at least four distinct granular and three distinct fibrillo-tubular elements forming a granulo-fibrillar conglomerate. This type of inclusions was formally termed the "stigmoid body" under the electron microscope. The stigmoid body is composed of the outer granulo-fibrillar and inner hyaloplasmic compartments. The immunoreactivity for hPAX-P2 is mainly localized to the former, especially to the low density granulo-fuzzy materials associated with the fibrillo-tubular elements. Identification of the ultrastructure of stigmoid body clarified their prevalence not only in the limbic and hypothalamic regions, but also in sex-steroid-sensitive peripheral tissues (e.g., peripheral sensory ganglia, ovary, testis) by consulting earlier electron-microscopic studies. Reviewing the history and nomenclature of this inclusion body, we reorganized the terminology of related neuronal cytoplasmic inclusions, the terms of which have often been confused, and discussed its functional significance on the basis of the present and previously accumulated data. In conclusion, we emphasized the importance of the stigmoid bodies in the sex-steroid-sensitive neural system because of their large size, high frequency, specific distribution in brains and peripheral tissues, effects of sex-steroids, and immunological and histochemical characteristics of the antibody marking the inclusion. The stigmoid bodies may provide a subcellular site for sex-steroid metabolism in their target tissues and play a critical role in cytosolic modulation of their actions (e.g., by aromatization) prior to their receptor binding.

The adaptor proteins HAP1a and GRIP1 collaborate to activate the kinesin-1 isoform KIF5C

“…2A for singly transfected cells). Puncta are likely related to an endogenous non-membranebound organelle formed by HAP1; within the hypothalamus, HAP1 is highly expressed (Chan et al, 2002;Li et al, 2003;Sheng et al, 2006) and associated with non-membrane-bound cytoplasmic bodies (Li et al, 1998;Shinoda et al, 1992Shinoda et al, , 1993Xiang et al, 2017) that sequester several key proteins in culture (Prigge and Schmidt, 2007;Rong et al, 2007;Sheng et al, 2008;Takeshita et al, 2011Takeshita et al, , 2006. When co-expressed in the same cells, GRIP1a and HAP1a are recruited to the same intracellular compartment (Fig.…”

Occurrence of glutamate receptor subunit 1–containing aggresome‐like structures during normal development of rat spinal cord interneurons

“…In these preliminary accounts, these inclusions received a wide variety of names, although there was no explanation of their functional significance. These examples included nucleoluslike bodies (Santolaya, 1973), nematosomes (Bourrat and Sotelo, 1983), dense granular cytoplasmic inclusions (Groves and Wilson, 1980), and stigmoid bodies (Shinoda et al, 1992(Shinoda et al, , 1993. Immunocytochemical characterization was only carried out in the last of these reports and showed that cytoplasmic inclusion exhibited positive immunoreactivity to aromatase.…”

“…In fact, retrospectively, it was found that proteincontaining inclusions with an identical structure had already been described in normal nerve cells in several species many years before (see for example Shinoda et al, 1993, for a detailed historical account). In these preliminary accounts, these inclusions received a wide variety of names, although there was no explanation of their functional significance.…”

“…Moreover, as with GluR1 containing inclusions, the number of stigmoid bodies seems to decrease as animals become older (Shinoda et al, 1992). Although the exact function of stigmoid bodies has not been clearly defined, it seems that they are related to changes in neuronal plasticity regulated by sex steroids (Shinoda et al, 1993).…”

Fine mapping ofAHI1as a schizophrenia susceptibility gene: from association to evolutionary evidence

“…A recent molecular finding in mice (96) shows that AHI1 interacts with Hungtingtin‐associated protein 1 ( Hap1 ), which is involved in intracellular trafficking and TrkB (tyrosine kinase type B) receptor internalization. AHI1 and Hap1 form stable protein complex structures identical to the stigmoid bodies seen in neurons where AHI1 has a preferential localization, hippocampus and brainstem (97). Stigmoid bodies have been suggested to be involved in many processes (RNA storage center, an inactive microtubule organizing center, vesicular trafficking, and a direct inhibitor of mitosis or a marker of postmitotic events; ref.…”