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How the γPKC activity is regulated in neurodegenerative spinocerebellar ataxia type 14 (SCA14)
Author(s) -
Aslam Naveed,
Alvi Farah
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1179.3
Subject(s) - purkinje cell , cerebellum , spinocerebellar ataxia , neurodegeneration , neuroscience , protein kinase c , stimulation , microbiology and biotechnology , biology , ataxia , chemistry , signal transduction , medicine , disease
The neurodegenerative spinocerebellar ataxia type 14 (SCA14) is linked with slowly progressive cerebellar ataxia accompanied by abnormal eye movements and slow slurred speech. The ataxic symptoms are due to loss of purkinje cells leading to cerebellar neurodegeneration. Recent observations directly link γPKC with SCA14 and its gene PRKCG is now widely recognized as a disease causing gene. γPKC is specifically expressed in brain and is highly expressed in purkinje cells. The SCA14 disease is characterized by degeneration of purkinje cells. Experimental observations indicate that γPKC can modulate the morphology and behavior of purkinje cells. Both positive and negative regulation of γPKC can be linked with changes in size and complexity of dendritic arbor in purkinje cells. Here, we investigate the question that how the activity of γPKC is regulated in purkinje cells of cerebellum? The growth of dendritic structure is strongly inhibited by γPKC activation. Here, we examine a proposal that γPKC activity in purkinje cells can be regulated through a DAG‐mediated molecular loop between γPKC and DGKγ. Our results show that γPKC activity in purkinje cells is regulated through a net negative feedback loop. Our results imply that on purinergic receptor stimulation the γPKC is activated through a sequence of DAG‐mediated molecular events. However, the γPKC restricts its own activation through a net negative feedback loop. Through our approach we are able to clarify the mechanism behind the spatiotemporal interaction of DAG effector molecules i.e. γPKC and DGKγ. Support or Funding Information BioSystOmics