Disease relevance of Slmap

• Sarcolemma-associated proteins implicated in muscular dystrophies revealed no differences on microarrays and were confirmed as normally distributed by immunofluorescence [1].

High impact information on Slmap

• Our inability to produce cell lines that stably expressed Slap suggested that Slap inhibited cell growth [2].
• Agents that specifically disrupt microtubules did not affect SLMAP association with centrosomes [3].
• Anti-peptide antibodies directed against SLMAP N-terminal sequences showed colocalization with gamma-tubulin at the centrosomes at all phases of the cell cycle [3].
• This observation suggests that lack of sarcolemma-associated dystrophin in Duchenne muscular dystrophy (DMD) muscle may result from enhanced degradation of truncated mutation products rather than their inability per se to associate with the sarcolemma [4].
• The cardiac-specific expression of SLMAP isoforms that can be targeted to distinct subcellular membranes, self assemble, and interact with the myofibril suggests a potential role for this molecule in the structural arrangement of the E-C coupling apparatus [5].

Biological context of Slmap

• Elevated levels of centrosomal SLMAP were found to be lethal, whereas mutants that lacked centrosomal targeting inhibited cell growth accompanied by an accumulation of cells at the G2/M phase of the cell cycle [3].
• These results imply that regulated levels and the temporal induction of SLMAP isoforms are important for normal muscle development [6].

Anatomical context of Slmap

• We have elucidated the genomic structure of a gene encoding the sarcolemmal membrane-associated protein (SLMAP), which encodes a 91 kDa polypeptide with a previously uncharacterized N-terminal sequence encompassing a forkhead-associated (FHA) domain that resides at the centrosome [3].
• A novel isoform of sarcolemmal membrane-associated protein (SLMAP) is a component of the microtubule organizing centre [3].
• The expression of SLMAP was developmentally regulated and its localization was distinctly apparent at the level of the membranes involved in regulating the E-C coupling mechanism [5].
• Dysfunctional SMAs were found to specifically upregulate the expression of a 35-kDa isoform of sarcolemmal membrane-associated protein (SLMAP), which is a component of the excitation-contraction coupling apparatus and implicated in the regulation of membrane function in muscle cells [7].
• Several SLMAP isoforms were expressed in the cardiac myocyte with unique COOH-terminal membrane anchors that could target this molecule to distinct subcellular membranes [5].

Other interactions of Slmap

• The Duchenne muscular dystrophy gene product "dystrophin" is a sarcolemma-associated cytoskeleton which is present just inside the sarcolemma [8].

Analytical, diagnostic and therapeutic context of Slmap

• Real-time PCR revealed high SLMAP mRNA levels in the db/db microvasculature, which were markedly downregulated during COOH treatment but elevated again when drug therapy was discontinued [7].
• We further investigated this issue by transiently expressing Slap by microinjection [2].

References