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Trafficking and assembly of gap junction proteins: My study in this area was devoted to developing novel approaches to understand mechanisms of assembly of gap junction proteins into channels. Factors that define the gap junction protein trafficking and assembly pathways in the intracellular compartments are not well established. I have engineered connexin constructs which interfere with gap junction channel assembly in a dominant negative manner.� These constructs demonstrated that intermixing between two different compatible connexins, Cx43 and Cx32, is a regulated processes (Das Sarma et al., 2001 [1]). I demonstrated for the first time that Cx43 and Cx32 are assembled in different intracellular compartments, where Cx32 oligomerizes into hexamers in the endoplasmic reticulum (ER), while connexin43 oligomerization is �one or more aspects of Golgi apparatus (Das Sarma et al., 2002 [2]). It is likely that a novel post-ER mechanism exist for the control of connexin assembly.� I also constructed a system using connexins fused to ER retention/retrieval motifs to trap assembly intermediates and to identify key steps in connexin-specific assembly pathways (Das Sarma et al., 2002 [3]). ER-retained constructs helped to further elucidate the mechanisms that regulate connexin assembly and provide the necessary tools to identify putative chaperones that participate as a co-factor in the assembly pathways (manuscript in preparation[4]).� My studies would benefit the field of gap junctions, specifically the general mechanisms of protein assembly.

Intercellular communication - MHV induced demyelination: MHV induced demyelinating model can be used as an experimental tool and gap junction proteins as a molecular component, to define novel pathways involved in MHV induced disease progression and CNS damage.�This allows for elucidation of the roles of gap junction intercellular communication in the progression of the chronic inflammatory demyelinating diseases. This model might provide insights and possible therapeutic targets to alleviate the progression of MS.

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Last updated on November 27, 2004. Jayasri Das Sarma, © Copy Rights Reserved.
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