Characterization of the nuclear lamina, nuclear pore complex and nucleocytoplasmic protein transport in a SCA7 model

• Recently alterations to the nuclear lamina, nuclear pore complexes (NPCs) and nucleocytoplasmic transport have emerged as a pathological mechanism in Huntington’s disease (HD). In this study, we investigated whether such a phenotype could also be detected in models of the hereditary disease Spinocerebellar ataxia type 7 (SCA7). This as both HD and SCA7 are caused by expansion of a polyglutamine domain in the respective disease protein and a common gain of function mechanism has been proposed for these disorders. Using an inducible SCA7 PC12 cell model and human SCA7 fibroblasts, we could not detect any nuclear lamina alterations, such as invaginations or Lamin B1 mislocalization, previously reported in HD. Unlike in HD models, we could also not detect any sequestration of nuclear pore proteins Nup62 or Nup153 into the polyglutamine aggregates formed by mutant ATXN7 in SCA7 cells. However, we could observe sequestration of the nuclear import receptor Importin β and increased cytoplasmic Ran levels in SCA7 cells. Despite this, no gross change in nuclear protein import could be observed. Taken together our data suggest that nuclear lamina, NPC and nucleocytoplasmic transport defects might not play the same early and/or central role in SCA7 pathology, as suggested in HD.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Neurodegeneration

Spinocerebellar ataxia type 7

Polyglutamine diseases

nucleoporins

nuclear lamina

nucleocytoplasmic transport

neurokemi med molekylär neurobiologi

Neurochemistry with Molecular Neurobiology

Publikations- och innehållstyp

vet (ämneskategori)

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