Collagen XVII is expressed in human CNS neurons

Seppänen, Allan; Autio–Harmainen, Helena; Alafuzoff, Irina; Särkioja, Terttu; Veijola, Johanna; Hurskainen, Tiina; Bruckner‐Tuderman, Leena; Tasanen, Kaisa; Majamaa, Kari

doi:10.1016/j.matbio.2005.11.004

Cited by 77 publications

(70 citation statements)

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“…Collagen XVII is a major structural component of the hemidesmosome (Has and Kern 2010), whereas collagen XXIII is associated with prostate cancer recurrence and distant metastases (Banyard et al 2007). However, membrane collagens XIII, XVII (Seppänen et al 2006), and XXV (Hashimoto et al 2002) are expressed in neurons, or neuronal structures, and collagen XXVIII is predominantly expressed in neuronal tissue (Veit et al 2006). New roles of collagens have been found in the development of the vertebrate nervous system, when collagen IV plays a role at the neuromuscular junction as a presynaptic organizer (Fox et al 2007(Fox et al , 2008.…”

Section: Functions Of Collagensmentioning

confidence: 99%

The Collagen Family

Ricard‐Blum¹

2010

Cold Spring Harbor Perspectives in Biology

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Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions. THE COLLAGEN SUPERFAMILYThe collagen superfamily comprises 28 members numbered with Roman numerals in vertebrates (I -XXVIII) ( Table 1). A novel epidermal collagen has been called collagen XXIX (Söder-häll et al. 2007), but the COL29A1 gene was shown to be identical to the COL6A5 gene, and the a1(XXIX) chain corresponds to the a5(VI) chain (Gara et al. 2008). The common structural feature of collagens is the presence of a triple helix that can range from most of their structure (96% for collagen I) to less than 10% (collagen XII). As described in the following discussion, the diversity of the collagen family is further increased by the existence of several a chains, several molecular isoforms and supramolecular structures for a single collagen type, and the use of alternative promoters and alternative splicing.The criteria to name a protein collagen are not well defined and other proteins containing one triple-helical domain (Table 2) are not numbered with a Roman numeral so far and do not belong to the collagen family sensu stricto.

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Section: Functions Of Collagensmentioning

confidence: 99%

The Collagen Family

Ricard‐Blum¹

2010

Cold Spring Harbor Perspectives in Biology

1,605

1,197

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“…Transmembrane collagen XVII, also known as BP180 or BPAG2, is widely expressed in skin (6)(7)(8), cornea (7,9), teeth (10), buccal and esophageal mucous membranes (7), brain (11), placenta, and umbilical cord (7). Among these tissues, collagen XVII plays the most important role in the skin, where it is a component of hemidesmosomes in basal keratinocytes and provides stable adhesion between the epidermis and the dermis.…”

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confidence: 99%

Ectodomain Shedding Generates Neoepitopes on Collagen XVII, the Major Autoantigen for Bullous Pemphigoid

Nishie

Lamer

Schlösser

et al. 2010

The Journal of Immunology

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As a type II transmembrane protein in basal keratinocytes, collagen XVII provides stable adhesion between epidermis and dermis in the skin. Its ectodomain can be shed from the cell surface, and autoantibodies in certain blistering diseases preferentially recognize the shed form. Major epitopes of collagen XVII are clustered within the juxtamembranous noncollagenous 16th A domain, and ectodomain shedding occurs within this region, suggesting that cleavage generates neoepitopes. However, the candidate cleavage sites have been controversial, and the mechanism of neoepitope generation is unclear. In this study, we investigated cleavage sites in the noncollagenous 16th A domain to understand the generation of neoepitopes and their pathological role. Polyclonal Abs recognizing the stretch Leu524-Gly532 preferentially reacted with the shed ectodomain, but not with the full-length form, indicating that a neoepitope was localized at this site. The neoepitope-specific Ab fixed complement and induced granulocyte-dependent dermal-epidermal separation in cryosections of normal human skin. The physiological cleavage sites were identified using mass spectrometry. N termini were found at Asp514, Leu524, Glu525, and Gly526, among which Asp514 and Glu525 were blocked by acetylation and pyroglutaminate. In silico prediction of B cell epitopes indicated that the antigenicity of the Leu524-Gly532 region increased substantially after shedding, regardless of the cleavage sites. Correspondingly, neoepitopes were found in the skin and blister fluids of patients with bullous pemphigoid, and bullous pemphigoid sera reacted with the peptide Leu524-Gly532. Taken together, these data demonstrate that physiological shedding of collagen XVII generates neoepitopes, which may serve as a target of blister-inducing autoantibodies.

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“…BP180 is strongly expressed in the cortex and hippocampus, regions of the brain that are predilection areas for e.g. Alzheimer's disease-related lesions 24 . In addition, the neuronal isoforms of BP230 are widely expressed in the human central and peripheral nervous 24,25 .…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer's disease-related lesions 24 . In addition, the neuronal isoforms of BP230 are widely expressed in the human central and peripheral nervous 24,25 . This, and BP's association of several neurological and psychiatric diseases, has led to a hypothesis that neuroinflammation could lead to a cross-reactive immune response between neural and cutaneous antigens 6,9,10 .…”

Section: Discussionmentioning

confidence: 99%

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

Försti

Jokelainen

Ansakorpi

et al. 2016

Journal of Investigative Dermatology

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Bullous pemphigoid (BP) is an autoimmune blistering skin disease with increasing incidence. BP is associated with neurological disorders, but it has not been established, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders is controversial. We conducted a retrospective nationwide study, using the Finnish Care Register for Health Care diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological and psychiatric comorbid disorders were evaluated for both groups, and associations were estimated by Cox regression and logistic regression analyses. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR=5.9, 95% CI 3.9-8.5). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR=2.7, 95% CI 2.0-3.5), and as a novel finding, also personality disorders (OR=2.2, 95% CI 1.3-3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, carry heightened risk for BP. Furthermore, several neurological diseases which cause central nervous system inflammation or degeneration were related to BP, and the association was strongest between MS and BP.Bullous pemphigoid (BP) is an autoimmune skin disease with incidence varying between 0.25 and 4.28/100.000 per year 1-3 . The age-adjusted incidence of BP has been reported to be on the rise 1-3 . BP typically presents with severe itching and blistering of the skin, but in up to 20% of patients blisters are completely absent and only excoriations or eczematous, urticated lesions are observed 4 . BP typically affects elderly people, has many comorbidities and carries an elevated risk of death compared with the general population of the same age [1][2][3][4] . The pathogenesis of BP is characterized by autoantibodies directed against the hemidesmosomal components between the basal keratinocytes of the epidermis and the extracellular matrix of the dermis, resulting in subepidermal blister formation. The main autoantigen is bullous pemphigoid antigen 180 (BP180, also known as BPAG 2 or collagen XVII), though BP patients may also have autoantibodies against bullous pemphigoid antigen 230 (BP230 or BPAG1), another hemidesmosomal protein 4 . Several studies have established an association between BP and neurological disorders, especially stroke, dementia and Parkinson's disease [5][6][7][8] . The mechanism behind this association has been suggested to be an autoinflammatory reaction against BP180 or the neuronal isoform of BP230 in the human brain 9,10 . However, previous studies did not specify the types of dementia or cerebrovascular stroke. Neurological disorders precede BP 5,6 , but it is unclear, whether the risk of developing neurological disorders is elevated after a diagnosis of BP.

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Collagen XVII is expressed in human CNS neurons

Cited by 77 publications

References 11 publications

The Collagen Family

The Collagen Family

Ectodomain Shedding Generates Neoepitopes on Collagen XVII, the Major Autoantigen for Bullous Pemphigoid

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

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