Shmukler B E, Bond C T, Wilhelm S, Bruening-Wright A, Maylie J, Adelman J P, Alper S L
Molecular Medicine Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Biochim Biophys Acta. 2001 Mar 19;1518(1-2):36-46. doi: 10.1016/s0167-4781(01)00166-x.
Small conductance calcium-gated K(+) channels (SK channels) are encoded by the three SK genes, SK1, SK2, and SK3. These channels likely contribute to slow synaptic afterhyperpolarizations of apamin-sensitive and apamin-insensitive types. SK channels are also widely expressed outside the nervous system. The mouse SK1 gene comprises at least 12 exons extending across 19.8 kb of genomic DNA. This gene encodes a complex pattern of alternatively spliced SK1 transcripts widely expressed among mouse tissues. These transcripts exhibit at least four distinct 5'-nucleotide sequence variants encoding at least two N-terminal amino acid sequences. Optional inclusion of exons 7 and 9, together with two alternate splice donor sites in exon 8, yields transcripts encoding eight variant C-terminal amino acid sequences for SK1. These include an altered putative S6 transmembrane span, modification of the C-terminal cytoplasmic domain binding site for calmodulin, and generation of two alternate predicted binding sites for PDZ domain-containing proteins. 20 of the 32 predicted mouse SK1 transcripts are expressed in brain at levels sufficient to allow consistent detection, and encode 16 SK1 polypeptide variants. Only four of these 16 polypeptides preserve the ability to bind calmodulin in a Ca(2+)-independent manner. Mouse SK1 also exhibits novel, strain-specific, length polymorphism of a polyglutamate repeat in the N-terminal cytoplasmic domain. The evolutionary conservation of this complex transcription pattern suggests a possible role in the tuning of SK1 channel function.
小电导钙门控钾离子通道（SK通道）由三个SK基因，即SK1、SK2和SK3编码。这些通道可能参与了对蜂毒明肽敏感和不敏感类型的缓慢突触后超极化过程。SK通道在神经系统之外也广泛表达。小鼠SK1基因至少包含12个外显子，跨越19.8 kb的基因组DNA。该基因编码了在小鼠组织中广泛表达的复杂的选择性剪接SK1转录本模式。这些转录本表现出至少四种不同的5'-核苷酸序列变体，编码至少两种N端氨基酸序列。外显子7和9的选择性包含，以及外显子8中的两个可变剪接供体位点，产生了编码SK1的八种变体C端氨基酸序列的转录本。这些包括推定的S6跨膜跨度的改变、钙调蛋白C端胞质结构域结合位点的修饰，以及为含PDZ结构域的蛋白质生成两个交替的预测结合位点。32种预测的小鼠SK1转录本中有20种在脑中的表达水平足以进行一致检测，并编码16种SK1多肽变体。这16种多肽中只有四种保留了以Ca(2+)非依赖性方式结合钙调蛋白的能力。小鼠SK1在N端胞质结构域的多聚谷氨酸重复序列中还表现出新颖的、品系特异性的长度多态性。这种复杂转录模式的进化保守性表明其在调节SK1通道功能中可能发挥作用。
