Caspase-9 Activation Revealed by Semaphorin 7A Cleavage Is Independent of Apoptosis in the Aged Olfactory Bulb

Ohsawa, Seiji; Hamada, Shin; Asou, Hiroaki; Kuida, K.; Uchiyama, Yasuo; Yoshida, Hiroki; Miura, Masayuki

doi:10.1523/jneurosci.4780-08.2009

Cited by 34 publications

(37 citation statements)

References 43 publications

(47 reference statements)

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“…Several families of axon guidance cues, including semaphorin 3a and Ephrin-As, have critical roles in the axonal wiring and the organization of the olfactory system. We have recently found that Sema7A, a membrane-anchored member of the semaphorin family of guidance proteins required for the proper formation of the lateral olfactory tract (13), is a substrate for caspase-9 (14). A rabbit polyclonal antibody against amino acid 1-100 of mouse Sema7A (Abcam) immunolabeled Sema7A specifically in caspase-9-activated cells (14).…”

Section: Resultsmentioning

confidence: 99%

“…We have recently found that Sema7A, a membrane-anchored member of the semaphorin family of guidance proteins required for the proper formation of the lateral olfactory tract (13), is a substrate for caspase-9 (14). A rabbit polyclonal antibody against amino acid 1-100 of mouse Sema7A (Abcam) immunolabeled Sema7A specifically in caspase-9-activated cells (14). To examine whether Apaf-1/caspase-9 signaling in OSN axons cleaved Sema7A during development, we performed immunofluorescent analysis of OB sections from WT, apaf-1-deficient, or caspase-9-deficient mice.…”

Section: Resultsmentioning

confidence: 99%

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Maturation of the olfactory sensory neurons by Apaf-1/caspase-9–mediated caspase activity

Ohsawa

Hamada

Kuida

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Although the apoptotic role of caspases has been largely understood, accumulating evidence in Drosophila suggests that caspases also control other processes than apoptotic cell death. However, how caspases contribute to the development of the mammalian nervous system remains obscure. Here, we provide unique evidence that Apaf-1/caspase-9-mediated caspase signaling regulates the development of olfactory sensory neurons (OSNs), which includes axonal projection, synapse formation, and maturation of these neurons. This caspase signaling leads to a cleavage of Semaphorin 7A, a membraneanchored semaphorin that is required for the proper axonal projection. Mutant mice deficient for apaf-1 or caspase-9 exhibit misrouted axons, impaired synaptic formation, and defects in the maturation of OSNs without affecting the number of these cells. Our findings suggest that Apaf-1/caspase-9-mediated nonapoptotic caspase signaling is required for the proper neural network formation during olfactory development.neural development | nonapoptotic function | axonal projection | synapse formation | Sema7A

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Maturation of the olfactory sensory neurons by Apaf-1/caspase-9–mediated caspase activity

Ohsawa

Hamada

Kuida

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, given that the release of SEMA7A to the medium by cleavage of its GPI anchor has been demonstrated to be essential in some processes (24), further autocrine activation of transmigrated PMNs by solubilized SEMA7A might be possible (25). Taken together, endothelial SEMA7A rises as a potential therapeutic target for the treatment of hypoxia-induced inflammatory disorders in the future.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Semaphorin 7A promotes neutrophil migration during hypoxia

Morote-García

Napiwotzky

Köhler

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

100

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Recent studies identified basic biological principles that are shared by the immune and the nervous system. One of these analogies applies to the orchestration of cellular migration where guidance proteins that serve as a stop signal for axonal migration can also serve as a stop signal for the migration of immune-competent cells. The control of leukocyte migration is of key interest during conditions associated with inflammatory tissue changes such as tissue hypoxia or hypoxic inflammation. Semaphorins are members of these axon guidance molecules. Previously unknown, we report here the expression and induction of semaphorin 7A (SEMA7A) on endothelium through hypoxia-inducible factor 1α during hypoxia. This induction of SEMA7A translates into increased transmigration of polymorphonuclear neutrophil granulocytes across endothelial cells. Extension of these findings demonstrated an attenuated extravasation of polymorphonuclear neutrophil granulocytes in Sema7a-deficient mice from the vasculature during hypoxia. Studies using chimeric animals identified the expression of Sema7A on nonhematopoietic tissue to be the underlying cause of the observed results. Taken together, our findings demonstrate that neuronal guidance proteins do not only serve as a stop signal for leukocyte migration but also can propagate the extravasation of leukocytes from the vascular space. Future antiinflammatory strategies might be based on this finding. endothelia | inflammation R ecent years have identified a close link between hypoxia and inflammation (1). Similar to an acute inflammatory response, hypoxia is marked by increased paracellular fluid exchange and the extravasation of immune-competent cells from the vascular space. Likewise, limited oxygen availability might be the product of the characteristic metabolic changes of inflammation leading to inflammation-associated hypoxia. In addition, proinflammatory cytokines that are released upon stimulation of the immune system might also be part of the hypoxia-enhanced expression of the transcription factor NF-κB (2). Neuronal guidance proteins (NGPs) notably mitigate the course of this process (3-5). For example, cues initially reported to guide neuronal growth and migration, such as netrin-1 or the repulsive guidance molecule (RGM)-A, reduce inflammatory tissue changes (4-6).A member of these NGPs are the semaphorins, a large family of secreted and cell-surface proteins recently found to modulate neurite extension. A member of this family, Semaphorin 7A (SEMA7A), holds the ability to induce the production of cytokines in macrophages and monocytes, which play a significant role during the effector phase of the inflammatory immune response (7,8). Furthermore, SEMA7A also stimulates cytoskeletal reorganization in melanocytes and monocytes, which translates into cell morphology changes that can result in spreading and migration of these types of cells (9-11). However, to date, the role and expression of SEMA7A during hypoxia was unknown.On the basis of these observations, we examined the in...

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“…The pleiotropic nature of semaphorins is particularly evident for Sema7A, whose roles in immune function [74] and cancer biology [75,76,77] have been extensively studied. In addition, a few reports have addressed its role in neuronal development [78,79,80,81,82]. A study performed in our laboratory has revealed a role for Sema7A and its two receptors, PlexinC1 and β 1 -integrin, in the regulation of GnRH cell motility [24].…”

Section: Semaphorin Expression and Role In The Development Of The Olfmentioning

confidence: 99%

Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

Giacobini¹

2015

Neuroendocrinology

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The semaphorin proteins, which contribute to the morphogenesis and homeostasis of a wide range of systems, are among the best-studied families of guidance cues. Much recent research has focused on the role of semaphorins in the development and adult activity of hormone systems and, reciprocally, how circulating reproductive hormones regulate their expression and function. Specifically, several reports have focused on the molecular mechanisms underlying the effects of semaphorins on the migration, survival and structural and functional plasticity of neurons that secrete gonadotropin-releasing hormone (GnRH), essential for the acquisition and maintenance of reproductive competence in mammals. Alterations in the development of this neuroendocrine system lead to anomalous or absent GnRH secretion, resulting in heterogeneous reproductive disorders such as congenital hypogonadotropic hypogonadism (CHH) or other conditions characterized by infertility or subfertility. This review summarizes current knowledge of the role of semaphorins and their receptors on the development, differentiation and plasticity of the GnRH system. In addition, the involvement of genetic deficits in semaphorin signaling in some forms of CHH in humans is discussed.

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Caspase-9 Activation Revealed by Semaphorin 7A Cleavage Is Independent of Apoptosis in the Aged Olfactory Bulb

Cited by 34 publications

References 43 publications

Maturation of the olfactory sensory neurons by Apaf-1/caspase-9–mediated caspase activity

Maturation of the olfactory sensory neurons by Apaf-1/caspase-9–mediated caspase activity

Endothelial Semaphorin 7A promotes neutrophil migration during hypoxia

Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing Hormone Development and Function

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