An unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the C. elegans putative aminophospholipid translocases.
An unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the C. elegans putative aminophospholipid translocases.
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DOI：
10.1186/1471-213x-8-96
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发表时间：
2008-10-02
影响因子：
--
通讯作者：
Schlegel RA
中科院分区：
文献类型：
--
作者：
Lyssenko NN;Miteva Y;Gilroy S;Hanna-Rose W;Schlegel RA
亚家族IV中的P型ATP酶是专门的真核跨膜蛋白，其已经被提出将氨基磷脂磷脂酰丝氨酸和磷脂酰乙醇胺从质膜的外表面直接转运到细胞表面单层。真核生物基因组包含许多编码该亚科成员的基因。目前还不清楚为什么每个生物体中有这么多这种基因，或者这些基因在生物体发育中起着什么样的作用。我们系统地研究了秀丽隐杆线虫基因组中编码的6个，达特-1至6，IV亚家族P-型ATP酶基因的表达和发育功能。达特-5是该组中唯一普遍表达的必需基因。达特-6是达特-5的一种转录较差的最近复制物。达特-2至Tat-4表现出组织特异性发育调节表达模式。达特-2和达特-4两者的强表达发生在肠和消化系统的某些其它细胞中。这两种蛋白也在子宫、精子发生和完全形成的受精囊中表达。达特-2单独在咽腺细胞、排泄系统和发育中的外阴的少数细胞中表达。达特-3的表达模式与达特-2和达特-4的表达模式几乎完全不同。达特-3表达可在类固醇生成组织中检测到：皮下组织和XXX细胞，以及咽的大多数细胞（除腺体外）、生殖系统的各种组织（除子宫和受精囊外）和缝细胞。在正常条件下，达特-1至tat-4的缺失很少或根本不干扰生物体生长和发育的正常进程。然而，在甾醇饥饿期间，达特-2至4成为生殖生长所必需的。达特-5可能编码常规地执行所提出的氨基磷脂移位酶功能的管家蛋白。虽然达特-1到tat-4是独立的，但看起来至多只是部分冗余。达特-2至4的表达模式和甾醇剥夺超敏性缺失表型表明，这些基因执行微妙的代谢功能，如微调消化或类固醇生成组织中的甾醇代谢。这些发现揭示了一个意想不到的高度专业化和广泛参与甾醇代谢的基因编码的推定氨基磷脂移位酶。
P-type ATPases in subfamily IV are exclusively eukaryotic transmembrane proteins that have been proposed to directly translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine from the exofacial to the cytofacial monolayer of the plasma membrane. Eukaryotic genomes contain many genes encoding members of this subfamily. At present it is unclear why there are so many genes of this kind per organism or what individual roles these genes perform in organism development. We have systematically investigated expression and developmental function of the six, tat-1 through 6, subfamily IV P-type ATPase genes encoded in the Caenorhabditis elegans genome. tat-5 is the only ubiquitously-expressed essential gene in the group. tat-6 is a poorly-transcribed recent duplicate of tat-5. tat-2 through 4 exhibit tissue-specific developmentally-regulated expression patterns. Strong expression of both tat-2 and tat-4 occurs in the intestine and certain other cells of the alimentary system. The two are also expressed in the uterus, during spermatogenesis and in the fully-formed spermatheca. tat-2 alone is expressed in the pharyngeal gland cells, the excretory system and a few cells of the developing vulva. The expression pattern of tat-3 is almost completely different from those of tat-2 and tat-4. tat-3 expression is detectable in the steroidogenic tissues: the hypodermis and the XXX cells, as well as in most cells of the pharynx (except gland), various tissues of the reproductive system (except uterus and spermatheca) and seam cells. Deletion of tat-1 through 4 individually interferes little or not at all with the regular progression of organism growth and development under normal conditions. However, tat-2 through 4 become essential for reproductive growth during sterol starvation. tat-5 likely encodes a housekeeping protein that performs the proposed aminophospholipid translocase function routinely. Although individually dispensable, tat-1 through 4 seem to be at most only partly redundant. Expression patterns and the sterol deprivation hypersensitivity deletion phenotype of tat-2 through 4 suggest that these genes carry out subtle metabolic functions, such as fine-tuning sterol metabolism in digestive or steroidogenic tissues. These findings uncover an unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the genes encoding the putative aminophospholipid translocases.