Turkiye Klinikleri Journal of Medical Sciences

.: REVIEW
Mikrotübül Yapı, Organizasyon ve Hataları: Spinal Müsküler Atrofi ve Amyotrofik Lateral Skleroz
Microtubule Structure, Organization and Defects: Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis
Gamze BORAa, Dila KOYUNOĞLUa, Merve SUNGUROĞLUa, Hayat ERDEM YURTERa
aTıbbi Biyoloji AD, Hacettepe Üniversitesi Tıp Fakültesi,
Ankara, TÜRKİYE
Turkiye Klinikleri J Med Sci. 2019;39(2):221-30
doi: 10.5336/medsci.2018-63881
Article Language: TR
Full Text
ÖZET
 Mikrotubuller, mikrofilamentler ve ara filamentler ile birlikte hucre iskeletini oluşturmaktadır. Alfa ve beta tubulin proteinlerinin biraraya gelmesiyle oluşan mikrotubuller, ici boş ve silindirik yapılar olup dinamik ozellik gostermekte, polimerizasyon ile uzamakta, depolimerizasyon ile kısalmaktadır. Mikrotubullerin yapısal duzenlenmesinde, farklı tubulin izotiplerinin yanı sıra tubulin post-translasyonel modifikasyonları (asetilasyon, detirozinasyon vb) ile mikrotubule bağlanan proteinler (MAP1B, TAU, statmin vb) rol oynamaktadır. Mikrotubuller hucre morfolojisinin belirlenmesi, hucre icinde organel, vezikul ve makromolekullerin (RNA, protein) taşınması, hucre bolunmesi, hucre farklılaşması ve hucre gocunde gorev almaktadır. Bu nedenle, mikrotubul iskeletinin doğru kurulması, korunması ve yapısının duzenlenmesi farklı hucresel fonksiyonların yerine getirilebilmesi icin gereklidir. Noronlar gibi uzun omurlu ve ozelleşmiş morfolojiye sahip hucrelerde ise mikrotubul stabilitesinin korunması yapı ve fonksiyon acısından onem taşımaktadır. Son yıllarda yapılan calışmalarda, mikrotubul iskelet hatalarının farklı norodejeneratif hastalıkların patomekanizmasında yer aldığı ve ortak olarak akzonal transportun bozulduğuna dair bulgular elde edilmiştir. Saptanan hataların, tubulin ya da mikrotubul ile ilişkili proteinleri kodlayan genlerdeki mutasyonların yanı sıra bu proteinlerdeki ifade veya post-translasyonel modifikasyon değişiklikleri nedeniyle ortaya cıkabileceği saptanmıştır. Bu derlemede, mikrotubullerin yapısı ve organizasyonunu duzenleyen temel mekanizmalar ozetlenmiş, ayrıca mikrotubul iskeleti hatalarının gorulduğu norodejeneratif hastalıklara ornek olarak Spinal muskuler atrofi'ler (proksimal SMA, SMALED1 ve SMALED2) ve Amyotrofik lateral skleroz'a (ALS) ait literaturde yer alan bulgular sunulmuştur.

Anahtar Kelimeler: Tübülin; mikrotübüller; SMA; ALS
ABSTRACT
 Microtubules are one of the basic elements of the cytoskeleton together with microfilaments and intermediate filaments. Microtubules are hollow cylindrical structures, which are formed by alpha and beta-tubulin proteins. Microtubules are dynamic structures, which grow by polymerization and shrink by depolimerization. Structure of microtubules is regulated by different tubulin isotypes as well as post-translational modifications of tubulin (acetylation, detyrosination etc.) and microtubule-regulating proteins (MAP1B, TAU, stathmin, etc.). Microtubules plays role in cellular morphology, intracellular organelle, vesicle and macromolecules (RNA, protein) transport, cell division, cell differentiation and cell migration as well. Therefore, the correct establishment and maintanence of microtubule structure are necessary for the different cellular functions. Maintanence of microtubule stability is structurally and functionally important for long-lived cells having specialized morphology like neurons. Recent studies have shown that microtubule defects are involved in the pathomechanism of different neurodegenerative diseases. Impaired axonal transport has been proposed as a common mechanism for such diseases. Microtubule defects can occur due to mutations in genes encoding tubulin or associated proteins as well as changes in expression or post-translational modifications of these proteins. In this review, the basic mechanisms which regulate microtubule structure and organization are summarized together with its defects in neurodegenerative diseases; spinal muscular atrophies (proximal SMA, SMALED1 and SMALED2) and amyotrophic lateral sclerosis (ALS).

Keywords: Tubulin; microtubules; SMA; ALS
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Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

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-During various attacks to the website,

-Disruption of the website because of a virus.

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Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

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